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How To Manage And Live With Herpes

How To Manage And Live With Herpes Shows Herpes Sufferers How To Have Healthy, Happy Relationships Despite This Crippling Disease That Affects Millions Of New People Each Year. With This Simple-to-use Guide They Can Manage Herpes And Enjoy Love. Youre about to: Find out how to get rid of embarrassing sores and blisters and never suffer the embarrassment of looking like a zombie again. Discover how to keep those nasty outbreaks at bay with powerful natural remedies. Discover how to identify the 9 types of herpes and sleep better at night without fear of transmitting herpes. Understand why you have frequent herpes outbreaks. Re-invent your sex life and manage herpes simplex. Stop it from managing you! Learn about the one thing you Must know if you want to have 100% safe sex moving forward. Never feel guilty about infecting a partner again.

How To Manage And Live With Herpes Summary


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Human cytomegalovirus

In the vast majority of infections with human cytomegalovirus symptoms are either absent or they are mild. In a pregnant woman, however, the virus can infect the placenta and then the foetus, for whom the consequences may be serious. In the US about one per cent of babies are born infected with the virus (about 40 000 per year). In about seven per cent of these there is evidence of virus-induced damage at birth, including small brain size and enlargement of the liver and spleen. In other individuals damage develops at a later stage the damage may be manifest in a number of ways, such as hearing loss and mental retardation. Human cytomegalovirus can also cause severe disease (e.g. pneumonitis, hepatitis) in immunocompromised patients such as those with AIDS, those who have received treatment for cancer and those who are immunosuppressed because they have received an organ transplant.

Herpes Simplex Keratitis

Herpes simplex keratitis is a common corneal ulceration caused by the herpes simplex virus (HSV). c. Treatment. Treatment of herpes simplex includes topical application of idoxuridine 1 percent (Stoxil ) drops or ointment as prescribed by a doctor. It is necessary to be cautious when administering this drug to pregnant women or women of childbearing potential. If no signs of healing are apparent within three to five days, debridement is done with a cotton-tipped applicator. If healing is not apparent within a week, refer the patient to ophthalmology.

Herpes Zoster Ophthalmicus

He reports that he has had similar episodes in the past that were treated with an antiviral drug. His records indicate that he suffered the first attack at the age of seven, ar which time his condition was diagnosed and treated as a severe follicular keratoconjunctivitis his records also indicate a history of recurrent episodes of herpes iabialis. Trifluorothymidine and acyclovir are effective steroids are contraindicated.

Cytomegalovirus Retinitis

Cytomegalovirus Retinitis

CMV is one of the most puzzling members of the Herpesviridae family. Ocular involvement has been reported during congenital infection and in patients with acquired immunodeficiency syndrome (AIDS) 34 . Primary infection satellite infiltrates. The optic disk is rarely infiltrated initially, but papillitis may be observed when retinitis progresses toward the posterior pole. Mild vitritis is associated with minor anterior segment inflammation. Despite slow progression of retinitis, destruction of the entire retina occurs within 3-6 months in the absence of anti-CMV therapy. Cicatricial lesions are at-rophic retina with vessel rarefaction. Fluores-cein angiography may be helpful in complex cases, when other differential diagnoses such as retinochoroidal toxoplasmosis, candida en-dophthalmitis, syphilitic retinitis, herpes simplex and herpes zoster retinitis are suspected.

Recurrent Herpes Simplex Secondary Herpetic Lesions

Recurrent Herpes Simplex Impetigo

The herpes simplex virus may be reactivated (recurrent) in an extraoral form on the lips or, inside the mouth, in an intraoral form. a. Extraoral Herpes. Cold sore blisters, also called herpes labialis (figure 1-8), are often associated with colds, trauma, fatigue, fevers, and prolonged exposure to the sun and the wind. The common site of occurrence is on the lips at the border with the skin of the face (called the vermilion border). The lesions usually consist of clusters of small vesicles that, in the early stage, contain a clear, transparent fluid. After a few hours, the vesicles rupture and form a crust or scab. The disease is self-limiting and usually disappears in 10 to 14 days. The individual is infective until complete healing has occurred. NOTE Cold sore blisters on the upper lip of this patient are caused by the herpes simplex virus. This recurring infection may be activated by prolonged exposure to sunlight and or wind. Figure 1-8. Extraoral herpes. b. Intraoral Herpes....

Primary Herpetic Gingivostomatitis

Initial exposure to the herpes simplex virus results in a generalized oral inflammation followed by vesicle formation and subsequent ulceration. Systemic symptoms of generalized illness accompany this initial attack. Most individuals have their primary exposure to this virus as infants however, this disease may also occur in young adults and elderly patients. This condition is contagious. Healing occurs spontaneously with the virus remaining in the nerve tissue, lying dormant in a latent form. Future recurrence of the condition may be either intraoral or extraoral.

Introduction to herpesviruses

The herpesviruses derive their name from the Greek word herpein, meaning to creep. More than 100 herpesviruses have been isolated from a range of hosts that includes mammals, birds, fish, reptiles, amphibians and molluscs. Eight of these viruses are human viruses (Section 11.2). A notable characteristic of herpesviruses is that, once they have infected a host, they often remain as persistent infections for the lifetime of the host. These infections are often latent infections, which can be reactivated from time to time, especially if the host becomes immunocompromised. Both primary and reactivated herpesvirus infections can either be asymptomatic or can result in disease of varying severity. The outcome depends on the interplay between the particular virus and its host, and especially on the immune status of the host.

The herpesvirus virion

Herpesviruses have relatively complex virions composed of a large number of protein species organized into three distinct structures capsid, tegument and envelope (Figure 11.2). The virus genome is a linear dsDNA molecule, which varies in size within the herpesvirus family from 125 to 240 kbp. The DNA is housed in the capsid, which is icosahedral, and the capsid is surrounded by the tegument. The HSV-1 tegument contains at least 15 protein species and some virus mRNA molecules. The envelope contains a large number of spikes (600-750 in HSV-1) composed of ten or more glycoprotein species. There are several different sizes of spike. A number of schemes have evolved for the nomenclature of herpesvirus proteins, with the result that an individual protein may be referred to in the literature by two or more different names. Most of the structural proteins are commonly named VP (virus protein). In HSV-1 the most abundant proteins in the capsid and the tegument are VP5 and VP16, respectively....

Herpes simplex viruses 1 and

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) initially infect epithelial cells of the oral or genital mucosa, the skin or the cornea. The virus may enter neurones and may be transported to their nuclei, where they may establish latent infections. HSV-2 is the usual causative agent of genital herpes, which is a sexually transmitted disease. In newborn

Cytomegalovirus CMV Antibody Test

Cytomegalovirus is a human viral pathogen that belongs to the herpes virus family. This virus causes serious illness in people with AIDS, in newborns, and in individuals being treated with immunosuppression therapy. CMV is the most common cause of posttransplant infection. The most severe form of CMV infection is seen in congenital infections. Infected newborns can exhibit permanent damage such as microcephaly, hydrocephaly, and chronic liver disease. Newborn diagnosis of CMV infection can be ac


Cytomegalovirus (CMV) is a ubiquitous DNA virus and one of the 7 human herpesviruses. It is present in many bodily fluids and is transmitted from person to person across the placenta, in breast milk, in child care centres, from communal living, from close personal contact, in blood transfusion and in transplanted organs.

Family Herpesviridae

The herpesviruses, of which more than 100 are known, infect vertebrates. A partial listing of these viruses is given in Table 6.6, together with their hosts and the diseases they cause. Most herpesviruses infect mammals or birds, but reptilian, amphibian, and fish herpesviruses exist as well. The viral genome is large, 120-230 kb, and the viruses encode many dozens of proteins, which allows them to finely regulate their life cycle. Virions are enveloped, 100-300 nm in size, with an icosahedral nucleocapsid (Figs. 2.1 and 2.16). Herpesviruses are ancient viruses that have coevolved with their vertebrate hosts. Phylogenetic trees of a number of viruses belonging the subfamily Alphaherpesvirinae are shown in Fig. 6.10. Figure 6.10A shows a tree of 14 viruses representing four genera. Genera Simplexvirus and Varicellovirus, both of which contain important human viruses as well as viruses of other animals, form well-defined taxa. Figure 6.10B compares the tree for four sim-plexviruses with...

Herpes Simplex Virus

Mucous Membrane With Herpes

HSV infection is a member of the herpesviridae family. Two serotypes of HSV have been identified HSV-1 and HSV-2. HSV-1 most often affects the mouth and is usually transmitted in childhood by contact with infected saliva. HSV-2 is generally herpes simplex hand, foot, and mouth disease rickettsialpox impetigo zoster immuno-globulin within 96 hr of exposure for naive patient otherwise, acyclovir, valacyclovir, famciclovir within 48-72 hr of rash Herpes zoster herpes simplex, associated with anogenital infection, and it usually is transmitted from anogenital or oral-genital sexual contact or transmission from a mother to her newborn. However, 14 to 47 of genital herpes results from HSV-1 (7). Thirty to fifty percent of pregnant women with a primary HSV outbreak transmit the disease to their newborn (8). Transmission generally occurs from skin-to-skin contact and introduction of the virus into the basal cell layers of susceptible mucosal surfaces. Following the primary infection, the...


Herpes simplex virus is a double-stranded, DNA-containing enveloped virus that causes a number of problems involving the skin, eye, oral mucosa, CNS, and genital tract. There are two types of herpes simplex virus, HSV-1 and HSV-2. HSV-1 may cause genital disease but more commonly causes nongenital infections of the mouth, lips, eyes, and CNS. HSV-2 is responsible for genital infections and neonatal infections and may cause oral lesions. Risk Factors Etiology. Genital herpes is usually caused by HSV-2 and is more commonly seen in teenagers and adults. It is transmitted by sexual activity. Presentation. Fever, regional adenopathy, and dysuria may be present in patients with primary genital herpes infection. Diagnostic Tests. The Tzanck stain may be performed on scrapings from the herpetic lesion. If herpes is present, then multinuclear giant cells and intranuclear inclusions will be detected. ELISA and immunofluorescent techniques may be useful. The diagnosis may also be...


Acyclovir is the most important of the available antiviral drugs. It has replaced vidarabine (ara-A), the first available antiviral agent for systemic use in serious infections. It is a synthetic purine nucleoside analogue, structurally related to guanosine. Its unique mechanism of action inhibits DNA synthesis and thus viral replication. It therefore does not affect the latent virus. There is a low incidence of development of resistance, but unwarranted use is unwise. The antiviral effects of acyclovir are particularly relevant for herpesviruses, as follows. It is especially effective against herpes simplex virus (HSV) types 1 and 2 ineffective against cytomegalovirus (CMV) (the related agent, ganciclovir, is however effective against CMV q.v.). The greatest value of acyclovir is in HSV encephalitis, in which trial results have shown a survival rate of about 80 and complete neurological recovery in about 50 . It is also of value in oral-labial, genital, rectal and neonatal HSV...

Herpes Simplex

Herpes simplex is a viral infection characterized by localized primary lesions, latency, and recurrence in the localized areas. There are two types of herpes simplex virus herpes simplex type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). HSV-1 is the causative agent for fever blisters and cold sores, as well as more serious diseases such as meningoencephalitis. HSV-2 is the causative agent for herpes genitalis, a sexually transmitted disease of the urogenital tract. Primary and recurrent infections may occur with or without symptoms. Painful, vesicular eruptions can occur on the skin and mucous membranes of the genitalia, anus, rectum, and mouth depending on sexual practices. Serologic identification of the specific HSV relies on tests that identify the type-specific antibody. Enzyme immunoassay and IFA are two tests that identify the presence of HSV antibodies in the blood. In addition to providing diagnostic information concerning HSV infections, HSV antibody testing is used...

Viral Genome Packaging Machines

Doughnut Packaging Packaging Structure

Virus assembly is a complex process that requires the temporal and coordinated activities of numerous proteins of both viral and host origin. Assembly pathways vary among the virus types, but common features are observed within certain groups. For instance, double-stranded DNA (dsDNA) viruses include the poxviruses, adenovirus, the herpesvirus groups, and many of the bacteriophages. Despite their obvious differences, common development pathways exist among these viruses, as follows. Infection of the host cell ultimately leads to the synthesis of capsid proteins that are assembled into procapsid structures. Concurrendy, viral DNA is replicated producing numerous copies of the viral genome. The assembly of an infectious virus requires that a single genome be packaged into the restricted confines of an empty procapsid. This extraordinary process represents the intersection of the capsid and DNA synthetic pathways, and is an essential step in virus assembly. Not unexpectedly, the details...

Bacteriophage Lambda Terminase and the Mechanism of Viral DNA Packaging

The developmental pathways of many double-stranded DNA (dsDNA) viruses, both prokaryotic and eukaryotic, are remarkably similar. In viruses as diverse as bacteriophage X and the herpesviruses, DNA replication proceeds through a rolling circle mechanism where the circular genome serves as a template for the synthesis of linear concatemers multiple genomes in length. Concurrendy, viral gene expression produces structural proteins, which self-assemble into procapsids and, in the case of the bacteriophage, tails necessary to assemble an infectious virion. Virus assembly requires that monomeric virion DNA molecules be produced from concatemers during packaging of the DNA into a procapsid. Thus, packaging represents the convergence of the DNA replication and capsid shell assembly pathways. Genome packaging in bacteriophage X has been extensively studied and this system has been used as a paradigm for virus assembly. Here we summarize current knowledge, present a working model, and indicate...

Model of DNA Cleavage and Packaging

A model for the maturation of capsids in herpesvirus-infected cells that is consistent with the current literature is depicted in Figures 2 and 4. The procapsid containing unprocessed scaffold proteins is depicted as the precursor to the angular type A, B, and C capsids found within cells infected with wild type viruses (Fig. 4). As described above, procapsids contain the unprocessed versions of the pUi26 and pUi26.5 gene products. It is believed that immature capsids are delivered via pUi,17 and pUL32-mediated transport to intranuclear replication compartments (not shown). 1. van Zijl M, Fairhurst J, Jones TR et al. Novel class of thiourea compounds that inhibit herpes simplex virus type 1 DNA cleavage and encapsidation Resistance maps to the UL6 Gene. J Virol 2000 74 9054-9061. 2. Krosky PM, Underwood MR, Turk SR et al. Resistance of human cytomegalovirus to benzimida-zole ribonucleosides maps to two open reading frames UL89 and UL56. J Virol 1998 72 4721-4728. 3. Underwood MR,...

DNA Packaging in Bacteriophage T4

The above represents an overall pathway for DNA packaging in T4, which, in many respects, is a common DNA packaging pathway among a number of well-characterized dsDNA phages. Common features among the dsDNA packaging phages include the dodecameric ring structure of the portal, a terminase complex formed by multiple copies of one small and one large subunit, the enzymatic functions associated with the terminase proteins, and the headful nature of the packaging process.2 Recent evidence suggests that the ATPase motifs in terminase are particularly well conserved among the phage packaging proteins,5 indeed, phage genomics reveals that these are among the signature proteins defining a phage quasi-species .6 The conservation appears to extend to the putative terminase from herpes viruses, which shows a particularly close resemblance to bacteriophage T4.5'7 Thus, it is likely that the dsDNA bacteriophages and herpes viruses package DNA by a common mechanism. Phage T4, with its large genome...

Building a Protective Shell for Viral DNA

Like other large dsDNA viruses, P22 assembles a protein procapsid and then inserts the DNA chromosome into this preformed container (Fig. 1). This strategy appears to be common to all dsDNA bacteriophages as well as the Herpesviridae. The genes required to build the procapsid and fill it with DNA map in a contiguous cluster on the P22 chromosome (Fig. 2). The four critical protein players in this process in P22 are analogous to those in other dsDNA viruses coat, scaffold, portal and terminase (Table 1). The coat protein shells of P22 procapsids and virions have T 7 icosahedral symmetry (each procapsid contains 420 molecules of coat, less any that are replaced by portal), and three-dimensional reconstructions of both kinds of particles have been made from cryo-electron micrographs.11 15 Procapsids contain about 250 molecules of scaffolding protein in the interior, all of which leave at or before the time of DNA packaging.8,16 Scaffolding protein has essential roles in procapsid...

The Putative Terminase UL15 UL28 Ul33

It is logical to presume that herpesviruses encode a multisubunit functional homolog of bacteriophage terminases that specifically recognizes genomic ends within the DNA, links the DNA to the capsid, and mediates the packaging of DNA through the hydrolysis of ATP. Although the absence of an in vitro packaging system in HSV precludes definitive proof, a complex of the UlI 5 and Ul28 gene products is the most likely to fulfill the role of terminase at the present time. (The Ul28 protein was originally referred to as ICP18.582). If the Ul15 and Ul28 proteins were subunits of the HSV terminase it would be expected that they would interact with one another, transiendy associate with capsids, hydrolyze ATP, and specifically bind and cleave Pac DNA sequences. Although evidence is indirect in some cases, most of these activities have been associated with the products of UlI 5 and Ul28 and their homologs in other herpesviruses. Indirect evidence that the Ul28 and Ul15 proteins interact has...

Intranuclear Transport Proteins Ul17 Ul32

During infection with Herpes simplex virus 1, gene expression and DNA replication occur within globular intranuclear compartments termed replication compartments.99 At least four cleavage and packaging proteins, Ul6, Ul15, Ul32 and Ul33, accumulate in replication compartments at relatively early times after infection (6-8 hours).93'100 102 Moreover, capsids have also been observed to colocalize completely within replication compartments at these times.101 These results have led to the suggestion that DNA packaging occurs in replication compartments however, the mechanism by which capsids are directed to these compartments is not understood. Capsid transport is apparendy a regulated function inasmuch as aggregates of procapsids accumulate in cells infected with viruses containing temperature sensitive mutations within the viral protease.44 Upon shift to the permissive temperature, the procapsids mature and the resulting type A, B and C capsids redistribute away from regions containing...

The Portal Vertex UL6

It has long been recognized that absence of a functional HSV-1 Ul6 gene precludes cleavage of concatemeric viral DNA.44'56'65'68,69 A high degree of homology exists between Ul6 homologs encoded by herpesvirus family members indicating that the encoded proteins likely play similar roles in the life cycles of all herpesviruses. pU ,6 is a component of procapsids, types A, B and C capsids, and virions.53'56 Thus, the capsid association of pUi,6 is unaffected by scaffold loss, capsid angularization or DNA packaging, and strongly suggests that pUi,6 is an integral component of the capsid shell.

Capsid Maturation

Herpesvirus Assembly

During the herpesvirus cleavage packaging reaction, DNA is inserted into preformed capsids. Cleaved viral genomes are not detected in cells infected with viruses that fail to assemble capsids, suggesting that capsids contain essential parts of the cleavage packaging machinery.32 There are four morphologic types of capsids that can be distinguished by electron microscopic examination of thin sections of herpesvirus-infected cells, and they are designated procapsids and capsid types A, B, and C.33'34 The capsid shell of procapsids is morphologically distinct from all other capsid types and appears porous and roughly spherical by electron microscopy.33'35 Procapsids contain internal scaffold proteins. Capsid types A, B and C are more angularized icosahedrons of approximately 120 nm in diameter. Type A capsids consist of only the icosahedral shell, type B capsids contain the angular shell and a roughly spherical internal scaffold, and type C capsids contain DNA and lack the scaffold.34'36...


With its similarity to the putative herpes viral terminases and the presence of a single critical ATPase center (other terminases reportedly have two or more ATPase sites18'71'72), the proposed ATPase motor in the large terminase subunit gpl7 offers an excellent model to elucidate the DNA packaging mechanism. The collection of unique mutants generated by the powerful molecular genetic and biochemical approaches, including the very rare conditionally lethal mutants, offer a unique resource to dissect the molecular details of ATP energy transduction into mechanical movement of DNA. The data may also have broad implications to the general understanding of energy and signal transduction mechanisms. The ATP (GTP) consensus motif is apparendy one of the most common motifs found in genomes (up to 5-10 of all expressed proteins), and may represent one of the fundamental (and ancient) motifs in biological systems.73 Numerous ATPase (GTPase) systems and molecular motors use this motif to trap...


P22 virion assembly is one of the prototypic virus nucleic acid packaging systems. Its terminase, portal, scaffold, coat and head completion proteins have little sequence similarity to the analogous proteins of other well-studied dsDNA virus types, yet a perfect parallel exists between these P22 general functions and those of their analogs in other systems. This relationship suggests that either the large dsDNA viruses (perhaps including herpesviruses, and even iridoviruses and adenoviruses 4 45) have an extremely distant common ancestor from which all their DNA packaging machines are derived or that the procapsid DNA packaging strategy represents an optimal solution arrived at more than once during the evolution of bacterial and eukaryotic viruses.

Concluding Remarks

The phenomenology of bacteriophage SPP1 DNA packaging is well known and some of the molecular mechanisms involved are among the best understood in tailed phages systems. These include the terminase recognition and cleavage of its target sequence pac, the structure and function of the portal protein, the mechanism of headful sensor, and connector assembly. Other aspects of the DNA packaging process were not yet studied in detail like the terminase-procapsid interaction, the properties and assembly of the DNA translocating complex, or the mechanism of DNA translocation. A complete picture of the DNA packaging process requires knowledge of all these molecular mechanisms and their integration in the dynamics of the infected cell. An interdisciplinary approach combining genetics, biochemistry, structural biology and bacterial cell biology, on one side, and comparative analysis of the strategies used in different virus systems, on the other side, will undoubtedly be necessary to...

ATP Binding Site I

The consensus sequence of the Walker-A nucleotide binding motif, (G A)XXXXGK(T S), is present in a large number of enzymes capable of nucleotide binding and or hydrolysis. Two Walker-A motifs have been identified in gpl7,9,18 the N -terminus proximal SRQLGKT16M67 (Walker-Ai) and a centrally locatedTAAVEGKS299-306 (Walker-An). As shown recendy, Walker-Ai is highly conserved among all the four T4-family (T4D, RB49, KVP40, KVP20) terminase sequences (Fig. 3) as well as in numerous other phage terminases and herpes virus terminases.5'19 Extensive combinatorial mutagenesis analyses of this site revealed a striking conservation of its features. No substitutions were tolerated in the highly conserved GKT signature sequence of theT4 gpl 7 Walker-A, including the conservative substitutions G165A, K166R, andT167A19 (Fig. 4, also, see below).

Immune Interactions Immune Evasion

There are multiple mechanisms by which microbes can persist in the body and evade the immune system. Tolerance is defined as specific reduction in the response of the immune system to a given antigen.101,102 In the case of transplacental infection, the fetus develops a certain degree of tolerance to antigens to which it is exposed. The immune system of fetuses is rather incompletely developed in utero, and microorganisms survive easily. Cytomegalovirus infects the fetus transpla-centally and produces extensive damage to multiple tissues. After delivery, infants continue shedding virions for weeks to months because they are unable to destroy the virus. Other mechanisms include the production of superantigens that stimulate a large population of T cells, which then become deleted if the encounter occurs during early development. Exposure to massive amounts of antigen in the circulation can also lead to tolerance.2,98 Immunosuppression is a well-demonstrated phenomenon that occurs during...

Transmission of vertebrate viruses

Some viruses may be released from lesions, for example foot and mouth disease virus from lesions on the feet and in the mouth, papillomaviruses from warts, and herpes simplex virus from lesions on the lips. These viruses could be transmitted directly by contact between an infected host and a non-infected host, or they could be transmitted indirectly through contamination of the environment. Transmission of rabies virus, for example from dog to human, requires

Comparison of Icosahedral Viruses

A gallery of structures of viruses determined by cryoelec-tron microscopy is shown in Fig, 2,5, All of the images are to scale so that the relative sizes of the virions are apparent, The largest particle is the nucleocapsid of herpes simplex virus, which is 1250 A in diameter and has T 16 symmetry (the virion is enveloped but only the nucleocapsid is regular), The rotavirus and reovirus virions are smaller and have T 13, Human papillomavirus and mouse polyoma virus are pseudo-T 7, Ross River virus (family Togaviridae) is enveloped but has regular symmetry, with T 4, Several examples of viruses with T 3 or pseudo-T 3 are shown (dengue 2, flock house, rhino-, polio-, and cowpea mosaic viruses, of which dengue 2 is enveloped but regular and the rest are not enveloped), B19 parvovirus has T 1, The general correlation is that larger particles are constructed using higher triangulation numbers, which allows the use of larger numbers of protein subunits, Larger particles accommodate larger...

Glioblastoma Multiforme

A common cause of polyneuropathy in adults that is usually preceded by GI or respiratory infection or by specific illnesses such as Epstein-Barr, Campylobacter enteritis, and cytomegalovirus infection. Respiratory paralysis may occur, necessitating mechanical ventilation. p.235

Maturation Cleavages in Viral Structural Proteins

FIGURE 2.21 Gallery of budding figures of viruses representing several different families. (A) Thin section of a herpes simplex virion (Herpesviridae) in an infected Hep-2 cell. The particle is apparently coated with an inner envelope and is in the process of acquiring its outer envelope from the nuclear membrane. From Roizman (1969). (B) Row of SV5 virions (Paramyxoviridae) budding from the surface of a monkey kidney cell. Cross sections of the nucelocapsid can be seen within several of the particles. From Compans et al. (1966). (C) Influenza virions (Orthomyxoviridae) budding at the surface of a chicken embryo fibroblast. There are distinct projections on the surface of the budding virions, but not on the adjacent membrane. From Compans and Dimmock (1969). (D) Machupo virus (Arenaviridae) budding from a Raji cell. From Murphy et al. (1969). (E) Sindbis virus (Togaviridae) budding from the plasma membrane of an infected chicken cell. From Strauss et al. (1995). (F) Rubella virions...

Nucleocapsid assembly 821 Helical viruses

The genome enters the procapsid through a channel located at a site that will become one of the vertices of the icosahedron. Any enzymes involved in packaging the genome are located at this site. The procapsids of some viruses, including herpesviruses, are modified at this site by the insertion of a 'portal' composed of one or more protein species.

Principles and Components

The Tc-controlled transcription activator tTA, a fusion protein comprising the N-terminally located wild-type TetR fused to the transcription activation domain of protein 16 of the herpes simplex virus, VP16 (Fig. 1A). 2. A minimal (i.e., enhancerless) cytomegalovirus immediate early (IE) promoter fused to heptamerized tetO sequences, the cognate binding sites of TetR (Fig. 1B). This promoter construct is henceforth called Ptet-1 (3) (the variants of tTA-responsive promoters are collectively referred to as Ptet). Fig. 1. (see facing page) Tetracycline-controlled fusion proteins and their target promoters. (A) Fusions between TetR rTetR with domains capable of either activating or silencing transcription, respectively. tTA is a fusion protein between the Tet repressor of the Tn10 Tc resistance operon of E. coli consisting of 207 amino acids and the 128-amino acids long carboxyterminal portion of the transactivator protein VP16 from herpes simplex virus. In tTA2, the VP16 moiety of tTA...

Generating tTArtTA Mouse Lines for Tissue or Cell Type Specific Tet Regulation

In general, this is a disadvantage, and as long as we do not know more about promoters in the context of various chromatin settings, we will not be able to circumvent this problem predictably. However, there are positive aspects of this phenomenon. Since the insertion site affects not only the specificity of a promoter but also its activity, there will automatically be a selection for animals in which tTA rtTA is not overexpressed. Thus even strong promoters like the cytomegalovirus IE promoter have been used successfully to drive tTA and rtTA in transgenic mice (16). The second advantage is that, depending on the insertion site, promoters can gain artificial specificities, which sometimes restrict Tet regulation to just a subgroup of cells for which the promoter is specific. An example is the highly hepatocyte-specific tTA mouse line, TAlap-2, (16) generated with the liver-enriched activator protein (LAP) promoter (36). Thus, it can be foreseen that a number...

Studies With Transgenic Mice Revealing Regulatory Regions Of Genes Specifically Expressed in Megakaryocyte

In transgenic mice in which expression of the herpes simplex virus thymidine kinase gene was directed by the 5'-untranslated region of the human aIIb gene, reporter gene expression was restricted to megakaryocytes and multipotential erythroid-megakaryocytic progenitors, reflecting the expression pattern of human aIIb gene. Treatment of transgenic animals with gancyc-lovir (GCV) resulted in anemia and reversible thrombocytopenia associated with a decreased number of megakaryocytes (Tronik-Le Roux et al., 1995). Prolonged GCV treatment induced erythropenia in the transgenic mice. Assays of hematopoietic progenitor cells in vitro demon

Human Immunodeficiency Virus HIV1 HIV2 Acquired Immunodeficiency Syndrome AIDS Test

Infection with HIV-1 is most common in the United States and HIV-2 is predominantly reported in West Africa. An individual is diagnosed as having AIDS if he or she has contracted the human immunodeficiency virus and exhibits one or more of the specific signs or symptoms associated with AIDS. Some of these signs include various types of pneumonia, cancer, and fungal and parasitic infections. Specific diseases associated with AIDS are Kaposi's sarcoma, chronic cryptosporidiosis, wasting syndrome, extrapulmonary tuberculosis, and pulmonary cytomegalovirus infection.

Parvovirus replication

The small genome of a parvovirus can encode only a few proteins, so the virus depends on its host cell (or another virus) to provide important proteins. Some of these cell proteins (a DNA polymerase and other proteins involved in DNA replication) are available only during the S phase of the cell cycle (Figure 4.5), when DNA synthesis takes place. This restricts the opportunity for parvovirus replication to the S phase. Contrast this situation with that of the large DNA viruses, such as the herpesviruses (Chapter 11), which encode their own DNA-replicating enzymes, allowing them to replicate in any phase of the cell cycle.

Atypical Toxoplasma chorioretinitis

Unusual manifestations of ocular toxoplasmosis exist. Bilateral, multifocal, and extensive ocular toxoplasmosis can rarely occur, and these cases have usually been in immunocompromised individuals. Toxoplasmosis can mimic acute retinal necrosis (ARN), an explosively blinding chorioretinitis usually caused by herpes viruses. Rarely, toxoplasmosis can mimic viral acute retinal necrosis (Moshfeghi et al., 2004). Since diagnosis is usually made by clinical appearance alone, therapy is usually directed first against the herpes virus, and subsequently a broader differential is entertained if instituted therapy fails to stop progression of disease. An anti-Toxoplasma regimen may be instituted in severe posterior uveitis as empiric therapy.

HIV Associated Immunosuppression

CMV was among the most common opportunistic infections in patients with AIDS. Prior to HAART, CMV retinitis accounted for 75-85 of cytomegalovirus disease in patients with AIDS, with an estimated lifetime risk of CMV retinitis of 30 1 . Since the introduction of HAART, the incidence of CMV retinitis has dropped by 80 , and has stabilized at about 15 of the population at risk, mainly as an AIDS defining infection.

Gases Respiratory Care

The answer is d. (Goodnough, Am J Surg 159 602-609, 1990.) Cytomegalovirus (CMV) is harbored in blood leukocytes. CMV infection is endemic in the United States, and its prevalence increases steadily with age. While acute CMV infection may cause transient fever, jaundice, and hepatosplenomegaly in cases of large blood donor exposures, posttransfusion CMV infection (seroconversion) is not a significant clinical problem in immunocompetent recipients, and therefore blood is not routinely tested for the presence of CMV Posttransfusion non-A, non-B hepatitis, however, not only represents the most frequent infectious complication of transfusion, but is associated with an incidence of chronic active hepatitis up to 16 and an 8-10 incidence of cirrhosis or hepatoma or both. The etio-logic agent in over 90 of cases of posttransfusion hepatitis has been identified as hepatitis C.

Suicide Gene Therapy

The commonest type of cytotoxic gene therapy used in bladder cancer is based on the herpes simplex virus thymidine kinase (HSV-tk) gene. This enzyme converts a prodrug ganciclovir into the active metabolite ganciclovir monophosphate, which is then further phosphorylated by cellular kinases and inhibits DNA polymerase leading to cell death (Fig. 15.2). As the prodrug is nontoxic, the aim is to target cell killing to the tumor. Both viral and nonviral methods have been used to deliver the HSV-tk gene to ortho-topic bladder tumors in animal models. Intratu-moral injection of an adenovirus containing the HSV-tk gene together with intraperitoneal ganciclovir administration led to a threefold reduction in tumor growth over 21 days of treatment in one study, which was associated with improved survival 37 . Another group had similar results, with twofold reduction in tumor 1) The adenoviral vector (AdV) delivers the Herpes simplex thymidine kinase (TK) gene to its target tumour cell. 1) The...

Selective Tumor Cell Killing

Other viruses have been studied in bladder cancer that are not bladder specific but cancer cell specific. PV701 is an attenuated strain of Newcastle disease virus that has been shown in a phase I trial to have tolerable toxicity levels 52 . It has several favorable characteristics, such as lack of antigenic drift, absence of human-to-human transmission, and minimal toxicity. The virus infects cancer cells at doses 1000 times lower than normal cells. Currently investigators at University of Chicago Cancer Research Center are undertaking a phase I trial of intravesical administration of PV701 prior to cystectomy (W.M. Stadler, lead investigator). The herpes simplex virus G207 also shows potential and has been demonstrated to be effective in an ortho-topic bladder cancer model 53 . Histological studies showed no viral infection of normal urothelium or distant organs.

Other biological effects

Two papers have drawn attention to possible antiviral activity attributable to resveratrol. The first described inhibition of the replication of Herpes simplex virus (HSV) types 1 and 2 in a dose-dependent and reversible manner by targeting an early event in the virus replication cycle it was most effective when resveratrol was added within 1 h of infection, less effective if added 6 h later, and ineffective at 9 h post-infection. Cell-cycle delay at the S G2M interphase was noted as the likely site of action (Docherty et al. 1999). It also synergistically enhanced the anti-HIV activity of a number of nucleoside analogues in combating infection in peripheral white blood cells (Heredia et al. 2000). A third noted the ability of resveratrol selectively to inhibit two bacteria responsible for gonorrhoea and meningitis (Docherty et al. 2001).

Generation of Adenoviral Vectors by Homologous Recombination in Bacteria The AdEasy System

The general outline of the Ad-easy system is as follows The gene of interest is first cloned into a shuttle vector. Four types of shuttle vectors are available, with and without a cytomegalovirus (CMV) promoter polyadenylation site, and with and without separate CMV-driven green fluorescent protein (GFP) genes. The resultant (kanamycin-resistant) plasmid is linearized by digesting with the restriction endonuclease Pmel. Subsequently, this linearized vector and an (ampicillin-resistant) adenoviral backbone plasmid are cotransformed into E. coli BJ5183 cells. Two backbone plasmids are available differing in

Adjuvant Reactogenicity

Limiting reactogenicity of adjuvanted vaccines to a tolerable level for widespread administration to humans has been a critical problem in transition from animal models to the clinic. The first priority in formulation of MF59 was to ensure safety, thus a very conservative formulation based upon low-risk components has been utilized. Clinical testing with both influenza and herpes simplex virus (HSV) vaccines in more than 18,000 subjects have demonstrated minimal reactogenicity of these formulations and the adjuvant has been approved for both commercial use and for further testing in both infants and pregnant women.

Pathogenesis of Aneurysmal Disease

Chronic inflammation plays an important role in aneurysmal disease. Much of the vessel wall destruction is undoubtedly mediated by the inflammatory infiltrate composed of T cells, macrophages, B lymphocytes, and plasma cells, but the antecedent trigger for this cellular migration remains unclear. It has been suggested that aneurysmal disease is in fact an antigen-driven immune disease from work analyzing AAA disease. Proposed antigenic activators to subsequent inflammation include elastin, interstitial collagen, oxidized low-density lipoprotein, cytomegalovirus, and artery-specific antigenic proteins such as AAAP-40. Following T-cell antigen recognition, the inflammatory cascade begins, ultimately resulting in vessel wall degradation and progression to aneurysmal disease.

Introduction to emerging viruses

And reassortment result in new viable combinations of genes (Section 20.3.3) new strains of influenza A virus come into this category. Some 'new' viruses that are reported are actually old viruses of which mankind has recently become aware, such as Kaposi's sarcoma-associated herpesvirus (Chapters 11 and 22).

Inflammatory Abdominal Aortic Aneurysms

An early hypothesis suggesting the periaortic fibrosis was secondary to retroperitoneal blood leakage from tiny perforations in a previously noninflammatory aneurysm has been rejected. Similarly, other theories of an initial prodromal atherosclerotic AAA developing into an aneurysm of inflammatory type remain unproven. The suggested mechanism for this transformation is by either lymphatic vessel compression by the expanding aneurysm resulting in stasis, edema and subsequent fibrosis, or as a direct consequence of an inflammatory reaction between blood in the aneurysmal sac and the aortic wall. Viral infection with herpes simplex or cytomegalovirus has also been proposed as a causal factor, with evidence of their presence in the aortic wall proven by DNA polymerase reactions.

Virusassociated cancers in animals

A number of cancers in animal species have been found to be associated with viruses. Outbreaks of some of these diseases can have serious economic consequences in agriculture. A few examples are given here of animal cancers associated with retroviruses and a herpesvirus. Marek's disease in chickens is a lymphoma, similar to that caused by retroviruses, but the causative agent is a herpesvirus and the transformed lymphocytes contain multiple copies of the viral genome. Papillomaviruses, already discussed as causative agents of human cancers (Section 22.2), cause cancers in cattle, horses and rabbits.

Specific Discussion

The answers are 139-d, 140-a. Unilateral elevation of the hemidiaphragm can be seen as a result of an enlargement or displacement of an abdominal organ, a subpulmonic process such as effusion, loss of volume of the lung with lobar atelectasis or surgical resection, or hemidia-phragmatic paralysis. Diaphragmatic paralysis results from interruption of the phrenic nerve supply to the diaphragm. The most common cause is malignancy, such as bronchogenic carcinoma, or postsurgical trauma. Twenty percent of patients who undergo open heart surgery sustain injury to the phrenic nerve. Other causes of diaphragmatic paralysis include polio, herpes, infections, lead poisoning, pulmonary infarctions, pneumonia, mediastinitis, and pericarditis. The diagnosis of unilateral paralysis of the diaphragm is suggested by the finding of an elevated hemidiaphragm on the chest x-ray. With diaphragmatic paralysis, the negative pleural pressure tends to pull the paralyzed diaphragm upward. Normally...

Progressive Multifocal Leukoencephalopathy

No history either of a similar rash over his face or of any visual symptoms (to rule out herpes zoster ophthalmicus). Micro Pathology Vesicular skin lesions with herpes viral inclusions, i.e., intranuclear, acidophil inclusions with a halo around them (Gowdry type A inclusions) syncytial cells also seen. Discussion Herpes zoster of the geniculate ganglion, or Ramsay Hunt syndrome, presents as a vesicular rash on the pinna followed by ipsilateral LMN facial nerve palsy.

Interactions Of Viruses With Their Hosts

The virulence of a virus for its host depends in part on the epidemiology of the virus, how it gets from one host to another. The herpesviruses set up a lifelong infection in which they are effectively transferred once per generation. It is in the virus's interest not to incapacitate the host so that the host can pass it on perhaps 20 years later, and her-pesviruses cause minor illness or no illness in most humans. On the other hand, arboviruses must cause a viremia (virus circulating in the blood) high enough to infect an insect taking a blood meal. Because many of these viruses are RNA viruses that do not encode functions to ablate the immune response, rapid and vigorous replication is required to establish the viremia before immunity is established, and this is often harmful to the host because many cells are killed in the process. To take another example, respiratory viruses that are transmitted as

Transgenesis by Pronuclear Injection in Cancer Research

Certain promoter elements have stood out in cancer studies as highly successful in giving reproducibly strong expression. For ubiquitous expression, the cytomegalovirus (CMV) immediate early promoter has been widely used (14,15). Good examples of widely used and successful lineage-specific promoters are the E -immunoglobulin heavy chain gene enhancer promoter for the B-cell lineage (8), the mouse mammary tumor virus long terminal repeat and whey acid protein gene promoter for the mammary gland (16), and the human keratin 14 promoter for skin (17). It is likely that an increasing number of studies will involve the use of in vivo regulatable promoters. One successful example of such a system is the Tet-off regulated promoter series. In the presence of tetracycline, or its analog doxycyclin, a mutant form of

Emerging Technologies

Human tumors are characterized by frequent unbalanced chromosomal rearrangements (98). In some cases entire chromosomes can be lost (resulting in monosomy) or gained (resulting in trisomy). Smaller gains and losses such as deletions, duplications, and nonreciprocal translocations are also common. Many of these events occur recurrently in human cancers and are thought to be the result of selective pressure that is, these changes give the tumor clone a growth or survival advantage. Unbalanced chromosomal rearrangements can now be modeled in the mouse germline using ES cell technology. In order for deletions to be generated in ES cells, two different approaches have been developed. One approach, pioneered by Dr. John Schimenti and colleagues, involves introducing a herpes simplex virus thymidine kinase (TK) gene into the ES cell genome, irradiating the ES, and selecting the irradiated cells against TK expression using gancyclovir (99). A significant percentage of the resultant...

Pathogenesis And Immunity

Like the other herpesviruses, EBV may exist in either a latent or lytic state. However, the predominant mode of B-cell infection appears to lead to latency. Owing to the consistency of patterns of latent EBV gene expression seen in different cell types, these patterns have been categorized into type I typical of African Burkitt's lymphoma with EBER1-2 and EBNA1 expression, type II seen in NPC and HD with EBER1 2 and LMP1 2 expression, and type III seen in latent-transformed B cells with EBER1-2, EBNA1-6, and LMP1 2 expression.285 As noted previously, at least 10 latent EBV genes are active in EBV-transformed B cells, yet only a few are required for B-cell transformation.198 Of the latent genes, LMP1 is the only one that has been clearly shown to exhibit transforming func-tion.286 Although EBV-transformed B cells grow continuously in cell culture, they are normal diploid cells and unable to form tumors in nude mice and are therefore not considered malignant. African Burkitt's lymphoma...

Prevention And Control

As with the other herpesviruses, hygienic measures are not very effective in preventing EBV infection. The large number of healthy seropositive viral excreters in the population provides a constant source of infectious virus, and measures to minimize contact with infectious saliva are impractical. Since congenital EBV infection is not a clinical problem, isolation of seronegative mothers from seropositive excreters is not warranted. Although unproven, measures to curb holoendemic malaria may be useful in prevention of Burkitt's lymphoma in central Africa, and avoidance of salted fish in southern China may be useful in prevention of NPC.231,235 Ultimately, the development of an EBV vaccine may lead to decreased rates of Burkitt's lymphoma and NPC if administered to seronegative children in the endemic areas. Vaccine development has focused on the 350-kDa, major envelope glycoprotein (gp350), which is the major target of neutralizing antibodies in vivo.309 Gp350 subunit vaccines, as...

Alphabetical List of Tests

Cytomegalovirus Antibody Test Differential White Blood Cell Count Diffusing Capacity of the Lung Digital Subtraction Angiography Direct Coombs' Test Drug Testing, Urine Echocardiography Electrocardiography Electroencephalography Electromyography Imaging Hematocrit Hemoglobin Hepatitis A Hepatitis B Hepatitis C Herpes Simplex High-Density Lipoprotein Histoplasmosis Holter Monitor Test Human Chorionic Gonadotropin Human Immunodeficiency Virus Hyaline Casts, Urine Hysterosalpingography Indirect Coombs' Test Insulin

Treatment And Prognosis

The susceptibility of HHV-6 to antiviral drugs is likely similar to that of the related herpesvirus CMV. The nucleoside analogue, ganciclovir, and viral DNA polymerase inhibitors, cidofovir and foscarnet, may be useful in severe infection, as in the post-transplant setting, but have not been tested in a controlled manner. Although uncomplicated primary infection in childhood is self-limited, infection in immunocom-promised patients such as organ transplant may lead to life-threatening complications.

Toxigenic Ablation Of Melanotrophs And Corticotrophs

Ablation of selected cell populations in transgenic mice using a targeted toxigenic protein has been useful in cell-lineage studies and physiological studies of tissue function within a complex biological environment (58-61). The two most commonly used toxins have been diptheria toxin A chain (DTA) and herpes simplex virus type 1 thymidine kinase (HSV1-TK), although both have limitations. HSV-TK has the advantage of temporal control, because its toxicity in most mammalian cells is dependent on administration of a nucleoside-analog-substrate such as ganciclovir and subsequent incorporation of the phosphorylated product into replicating DNA strands. Recently however, DTA expression has been regulated more precisely using Cre-loxPtechnology (62), and refinements of this approach may increase its utility in ablation studies of postmitotic cells including neurons.

Constructing the Targeting Vector

The investigator has a number of choices with regard to targeting vector. The most widely used selection strategy employs the neo resistance gene (12). Other resistance genes may be used but the neo resistance cassette has been the most popular. Though the neo cassette provides a positive selection for insertion of the neo gene along with the targeted mutation, it does not discriminate between clones positive for homologous recombination and clones harboring a random or nonhomologous insertion of the targeting construct. To account for this, a second, negative, selection strategy is employed. This is the positive-negative selection strategy of Mansour et al. (13). The most commonly employed negative selection strategy uses the herpes simplex virus thymidine kinase (HSV-tk) gene cassette, expressing the HSV-tk gene, included to one side of the targeting vector. In a homologous recombination event, the HSV-tk gene is excised. However, in a random insertion event, HSV-tk is not excised...

Infections That Cause Cancer

Many infectious agents have been posited to cause cancer. The IARC biannually reviews epidemiologic and basic science information on putative cancer-causing agents. It then classifies these agents as definite, probable, possible, or unlikely causes of cancer. To date, they have carried out extensive evaluations of liver flukes, schistosomes, H. pylori, hepatitis viruses, human herpesvirus 8 (HHV-8), HPV, HTLV, human immunodeficiency virus (HIV), and Epstein-Barr virus (EBV Table 12-1). Certain infections may be important, but not sufficient, for the induction of cancer. Just as most smokers do not get lung cancer, most infections with potentially carcinogenic pathogens do not proceed to a malignancy. For example, the large and diverse group of HPVs is implicated in causation of a variety of proliferative conditions, some of which (warts, epithelial cysts, intraepithelial neoplasias, anogenital, orola-ryngeal and oropharyngeal papillomas, keratoacanthomas, and other types of...

Receptors for Virus Entry

Specific receptor (or perhaps a specific set of receptors) expressed on the cell surface, and both protein receptors and carbohydrate receptors are known. In some cases, unrelated viruses make use of identical receptors. A protein called CAR (Coxsackie-adenovirus receptor), a member of the immunoglobulin (Ig) superfamily, is used by the RNA virus Coxsackie B virus (Picornaviridae) and by many adenoviruses (Adenoviridae), which are DNA viruses. Sialic acid, a carbohydrate attached to most glycoproteins, is used by influenza virus (family Orthomyxoviridae), human coronavirus OC3 (family Coronaviridae), reovirus (Reoviridae), bovine parvovirus (Parvoviridae), and many other viruses. Conversely, members of the same viral family may use widely disparate receptors. Fig. 1.3 illustrates a number of receptors used by different retroviruses (family Retroviridae). These receptors differ widely in their structures and in their cellular functions. Where known, the region of the cellular receptor...

An 18monthold has failure to thrive and developmental delay The patient also has a history of recurrent ear infections

Before 1 mo of age Herpes zoster (shingles) two episodes or more than one Herpes simplex (ulcer 1 mo duration or pneumonia or Definition of Abbreviations AIDS acquired immunodeficiency virus CMV cytomegalovirus CT computed tomography HSV herpes simplex virus LIP lymphoid interstitial pneumonia MRI magnetic resonance imaging OFC occipitofrontal circumference OM otitis media PCR polymerase chain reaction. Modified from Centers for Disease Control and Prevention MMWR 43(RR-12) 1-19, 1994.

Experimental Viral Uveitis

Experimental models, but also in human diseases. Progress made in the study of both entities has led to improved therapeutic strategies. Animal models including rabbits, mice and guinea pigs have been developed to study her-petic ocular infections. Rabbits were used to induce CMV chorioretinitis i7 . Intracamerular injection of herpes viruses induced severe anterior uveitis in the injected eye and a moderate contralateral chorioretinitis after a period of 7-i0 days. The absence of posterior segment involvement in the injected eye remains unexplained. Intravitreal injection of an active viral preparation induces a total primary uveitis due to viral cytopathic effects, starting less than iweek after injection. Intraocular reintroduction of the virus, whatever its replicative potential may be, triggers secondary uveitis with an acute onset, associated with an immunopatho-logic reaction mediated by virus-specific T-lymphocytes. Based on interesting studies, viral propagation after...

Laser Resurfacing with the CO2 Laser

Cold Sore Crusting Stage

Infection by various microorganisms is a risk to any healing skin, including that following laser resurfacing. Generally, oral antibiotics are given for seven to ten days postoperatively. Antiviral medication is also given to prevent any activation of herpes simplex, the virus that causes cold sores. A cold sore allowed to erupt may spread to cover large areas of the face because the herpes virus grows well on de-epithelialized skin. Excessive viral growth can lead to scarring if it is not treated. Occasionally patients experience infections with candida, a type of fungus. This may necessitate treatment with an oral antifungal drug.

Acute Retinal Necrosis ARN

In 1971 Urayama and associates reported the first six cases of presumed viral retinal necrosis and called it unilateral acute uveitis with retinal periarteritis and detachment 60 . The disease is known in Japan as Kirisawa uveitis. Bilateral forms were described later by Western authors. Fisher et al. used the term acute retinal necrosis for the first time in 1982 18 . Later studies confirmed the role of VZV and HSV in the pathogenesis of ARN. In 1994, Holland and the American Uveitis Society unified the spectrum of presumed herpetic retinopathies and defined it as necrotizing herpetic retinopathies 32 .The prevalence of ARN is nearly equal in both sexes. The majority of cases occur in the 5th-7th decades of life. Viral retinitis may occur congen-itally, in newborns or in young children. It is still not known why the disease was not reported before the 1970s. Both healthy and immunocom-promised patients may develop ARN during either primary or recurrent herpes virus infection....

Constitutive Recombinase Expression

AMHC, a-myosin heavy chain CMV, cytomegalovirus IRBP, interphotoreceptor retinoid-binding protein MLC2v, myosin light chain 2v POMC, propiomelanocortin WAP, whey acidic protein ZP3, mouse zona pellucida 3 gene. aMHC, a-myosin heavy chain CMV, cytomegalovirus IRBP, interphotoreceptor retinoid-binding protein MLC2v, myosin light chain 2v POMC, propiomelanocortin WAP, whey acidic protein ZP3, mouse zona pellucida 3 gene. Fig. 6. Inducible systems. (A) Regulation of Cre expression by doxycycline. The reverse transactivator (rtTA) is expressed through a constitutive ubiquitous or cell type-specific promoter. Without doxycycline, the rtTA is inert and unable to activate Cre transcription. In the presence of doxycycline, rtTA binds to the tetO7 human cytomegalovirus (hCMV) promoter, leading to Cre expression. (B) Principle of the hormone-regulated Cre-steroid receptor ligand binding domain (LBD) fusion protein. Cre is fused to a mutant LBD, which is unresponsive to its natural ligand but can...

Vulvovaginal Infections

Medical Vulva Development

Varicella zoster virus (VZV) is a member of the herpes virus group. It persists in the body as a latent infection after the primary infection. Primary infection with VZV results in chicken pox (varicella). Herpes zoster (shingles) represents a one-time reactivation. VZV enters through the respiratory tract and conjunctiva. Herpes zoster (shingles) occurs when latent VZV resurfaces. Factors associated with recurrent disease include aging, immunosuppression, intrauterine exposure, and varicella infection at an early age. The eruption occurs unilaterally in the distribution of a dermatome supplied by a dorsal root or extramedullary cranial nerve sensory ganglion. Clinically, this is often seen on the trunk or the area of the fifth cranial nerve, but herpes zoster can appear on the buttock, perineum, and vulva (Fig. 2). Typically, two to four days prior to visible eruptions, patients report pain and par-esthesia in the involved area. This is followed by discrete urticarial plaques...

Atomic Structure of T3 Viruses

Virus And Atom Photos

FIGURE 2.5 Gallery of three-dimensional reconstructions of icosahedral viruses from cryoelectron micrographs. All virus structures are surface shaded and are viewed along a twofold axis of symmetry. All of the images are of intact virus particles except for the herpes simplex structure, which is of the nucleocapsid of the virus. Most of the images are taken from Baker et al. (1999), except the images of Ross River virus and of dengue virus, which were kindly provided by Drs. R. J. Kuhn and T. S. Baker. FIGURE 2.5 Gallery of three-dimensional reconstructions of icosahedral viruses from cryoelectron micrographs. All virus structures are surface shaded and are viewed along a twofold axis of symmetry. All of the images are of intact virus particles except for the herpes simplex structure, which is of the nucleocapsid of the virus. Most of the images are taken from Baker et al. (1999), except the images of Ross River virus and of dengue virus, which were kindly provided by Drs. R. J. Kuhn...

Historical Background

Adjuvants Vaccine

FIA has been included in veterinary, as well as human, vaccines. The veterinary vaccines included vaccines against foot-and-mouth disease (5), equine influenza virus (6), hog cholera (7), rabies (8), parainfluenza 3 (9), Newcastle disease (10), and infectious canine hepatitis (11). In cattle, FIA was inefficient in combination with herpesvirus (12). In humans, FIA was used for a period of about two decades, particularly with vaccines against influenza virus (13), tetanus toxoid (14), and killed polio-myelitis virus (15), whereas it failed to increase vaccine efficacy when used with adenovirus (16) and trachoma (17).

Is Livergen Suitable For Three Months Pregnancies

The answer is a. (Braunwald, 15 e, pp 1118-1134.) Human papillomavirus (especially subtypes 16, 18, and 31) has an established relationship to abnormal Pap smears and cervical dysplasia. HIV, Chlamydia, or herpesvirus infections are not directly associated with cervical dysplasia.

Lytic Infection or Latent Infection

In latent infections, no virus replication occurs. The best understood case of latent infection is that of temperate bac-teriophage, which express genes that repress the replication of the virus. Once the lysogenic state is established, in which viral replication is repressed, it can persist indefinitely. Among vertebrate viruses, many of the herpesviruses are capable of latently infecting specialized cells that are non-permissive or semipermissive for virus replication. As one example, herpes simplex virus type 1 establishes a lifelong, latent infection of neurons of the trigeminal ganglia. In this case it is thought that latent state arises because the neuron lacks cellular factors required for the transcription and replication of the viral DNA, rather than because of the production of a herpes protein that suppresses replication. Reactivation of the virus at times leads to active replication of the virus in epithelial cells innervated by the infected neuron, resulting in fever...

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Vulvodynia Inner Labia

Gardnerella vaginalis, 84 Genital anomalies imperforate hymen, 32, 33 longitudinal vaginal septum, 32 transverse vaginal septum, 32 vaginal agenesis, 31-32 vulvovaginal abnormalities, 34 Genital herpes virus infection, 3 Genital mucosa chronic ulcer of, 54 genetic, 55 Genital mutilation, 184 Genital staphylococcal infections, 85 Genital tuberculosis, 84 Genital warts, 4 therapy of, 75 Genitalia, ambiguous, 31 Granular cell tumors, 152-155 Granuloma inguinale, 79-80 Granuloma pyogenicum. See Pyogenic granulomas Haemophilus ducreyi, 81 Hailey-Hailey disease, 54 Hemangioma, 149-150 Hemophilus ducreyi, 4 Herpes simplex virus (HSV), 4, 73 infection, 69 of anogenital skin, 72 diagnosis of, 72 of mouth, 71 neonatal, 72 recurrent, 71 treatment, 72 serotypes of, 69 Herpes zoster, 69

Non Necrotizing Herpetic Retinopathies NNHR

This entity was reported recently 10 . Molecular analysis applied to ocular fluids confirmed the presence of herpes virus DNA in patients presenting with different forms of chronic and atypical posterior uveitis, such as Beh et's disease, retinal vasculitis and birdshot retino-choroidopathy. Non-necrotizing retinopathies associated with haemorrhages have been described (Fig. 10.7). The disease is usually bilateral. It is important to emphasize that all patients with NNHR are corticoresistant or corticode-pendent at a high level. The initiation of specific antiviral therapy improved ocular inflammation. Immunosuppressors were discontinued and steroids were significantly tapered. Evolution under therapy is close to that observed in herpetic keratouveitis and steroids cannot be interrupted.

Epidemiology The Spread Of Viruses From Person To Person

Many viruses are transmitted by sexual contact. Virus may be present in warts in the genital area (e.g., herpes simplex virus type 2 and human papillomaviruses) or in semen or vaginal secretions (e.g., HIV, hepatitis B virus). Infection begins in the genital mucosa but may spread to other organs. Because the opportunity for spread by sexual contact is much more restricted than for spread by other routes, viruses spread by sexual transmission almost invariably set up long-term persistent infections that cause only mild disease, at least early in infection. This allows the virus to be disseminated over long periods of time. Many viruses can be spread vertically. Congenital infection of the fetus in utero or during passage of the infant through the birth canal occurs with viruses such as HIV, cytomegalovirus (family Herpesviridae), and rubella virus (genus Rubivirus, family Togaviridae). Vertical transmission can also occur shortly after birth, by breast feeding for example. HTLV I...

Introduction to virus vaccines

Effective vaccines are in use to protect against diseases caused by many viruses such as polio, rubella, rabies and foot and mouth disease. This chapter will describe the various categories of virus vaccine that are in medical and veterinary use, and will outline some aspects of their manufacture. Effective vaccines have yet to be developed against many other viruses, including HIV-1, hepatitis C, Ebola and the herpes simplex viruses. Those involved in virus vaccine research face many difficulties, such as multiple antigenic variants of target viruses and the requirements for high standards of safety. Some vaccines that have been developed have not been accepted for widespread use because of safety concerns. The great need for new vaccines has spawned

Cold Sores And Fever Blisters

Small painful blisters on lips (or genitals) that break and form scabs. May appear after fever or stress. Caused by a herpes virus. They heal after 1 or 2 weeks. Holding ice on the sores for several minutes, several times a day may help them to heal faster. Putting alum, camphor, or bitter plant juices (see Cardon, p. 13) on them may help. No medications do much good. For information about herpes on the genitals, see p. 402 .

Structure of Other Enveloped Viruses with Icosahedral Nucleocapsids

The herpesviruses are large DNA viruses that have a T 16 icosahedral nucleocapsid (Fig. 2.5). A schematic diagram of an intact herpesvirion is shown in Fig. 2.16A. Underneath the envelope is a protein layer called the tegu FIGURE 2.16 Two views of herpes simplex virus. (A) Cutaway schematic representation showing the outer envelope with projecting spikes, the irregular inner margin of the envelope due to the tegument, and the icosahedral core containing 162 capsomeres in a T 16 arrangement. (B) Negatively stained electron micrograph of an intracellular particle without the outer envelope. One of the triangular faces of the icosahedron is outlined in red in each case. Adapted from Murphy et al. (1995, p. 114) and Dalton and Haguenau (1973, p. 92), respectively. FIGURE 2.16 Two views of herpes simplex virus. (A) Cutaway schematic representation showing the outer envelope with projecting spikes, the irregular inner margin of the envelope due to the tegument, and the icosahedral core...

Spread from the Portal of Entry

Lymphatic spread occurs in most cases once the organisms gain access to subepithelial tissues or serosal surfaces. Lymphatic vessels are distributed in most tissues of the body, with few exceptions such as the brain. Lymph is carried by lymphatic vessels to regional lymph nodes, where it circulates through the node and eventually returns to the systemic circulation through the thoracic duct and the great lymphatic vein. One to three liters of lymph is returned to the systemic circulation every day. Most pathogens are filtered in lymph nodes before reaching the systemic circulation, but some actually reproduce either in the endothelium of lymphatic vessels (e.g., Mycobacterium leprae)2,53 or in tissue macrophages present in the lymph nodes (e.g., Y. pestis and Brucella spp.) or lymphocytes (HIV and herpesviruses, including Epstein-Barr virus).54 Some organisms reach the systemic circulation after overwhelming the defenses in the lymph nodes (e.g., Bacillus anthracis and Y pestis)....

Loss of Function Experiments

Nique are exciting, a number of problems may limit its application in studies of the brain. Embryo lethality resulting from toxin expression in cells essential for embryo survival is clearly a potential hazard even where tissue-specific promoters are used, minimal ectopic expression may be sufficient to result in death caused by the potent nature of these toxins. The recent development of an attenuated DT-A gene (26), which requires a higher level of expression to produce a lethal effect, may prove to be a more versatile tool in genetic ablation experiments. Another problem with these studies regards the possibility that early ablation of one cell type may lead to abnormal development of other cells through the absence of cell interactions. Specificity of ablation may not be obtained and hence any loss of function would be uninterpretable. The use of an inducible toxic gene, such as tk from herpes simplex virus in transgene constructs (27), may circumvent the developmental side...

Vaccine Formulations and Delivery

Requires that the coding DNA for the candidate vaccine antigen be placed into a plasmid, usually containing a strong eukaryotic promoter such as cytomegalovirus. Purified plas-mid in saline is then injected intradermally or intramuscularly and transfection of cells occurs. The transfected cells produce the candidate antigen, which, being intracellular, is processed and then expressed on the cell surface via class I MHC. If the cell is lysed, additional candidate antigen is released, which can then be processed via the extracellular class II pathway, or the cross-presentation pathway (see Fig. 11-4). Thus, via this methodology it is possible to generate MHC class I- and MHC class II-dependent responses to the candidate antigen.

Transformation of Cells

The normal outcome of the infection of a cell by a virus is the death of the cell and the release of progeny virus. The major exceptions are the persistent infection of cells by retroviruses and the latent infection of cells by viruses such as herpesviruses, in which the cell survives with its properties little altered except for the new ability to produce virus. However, another possible outcome is the transformation of the cell, which involves not only the survival of the cell but an alteration in its growth properties caused by deregulation of the cell cycle. Transformed cells may be able to induce the formation of a tumor if they are produced within an animal or are injected into an animal after formation ex vivo. Transformation of a cell needs to be distinguished from tumorigenicity, the ability of the transformed cell to cause a tumor. Transformed cells may fail to cause a tumor because they are rejected by the host's immune system or because the transformed cells lack some...

The Nature of Viruses

It is obvious that viruses that have larger genomes and encode larger numbers of proteins, such as the herpesviruses (family Herpesviridae), have more complex life cycles and assemble more complex virions than viruses with small genomes, such as poliovirus (family Picornaviridae). The smallest known nondefective viruses have genomes of about 3 kb (1 kb 1000 nucleotides in the case of single-stranded genomes or 1000 base pairs in the

Differential diagnosis

Congenital toxoplasmosis must be differentiated from other possible causes of the classic clinical acronym 'TORCH' for a series of etiologies that share similar signs and symptoms. The acronym includes Toxoplasma, rubella, cytomegalovirus, syphilis, and herpes simplex virus. However, emerging pathogens such as West Nile Virus must be considered as part of any differential in known congenital infection (Alpert et al., 2003). Recurrent toxoplasmosis with its unilateral active lesion associated with multiple adjacent chori-oretinal scars with the appropriate clinical history is virtually pathognomonic. However, clinical syndromes such as serpiginous chorioretinitis, and other infectious etiologies such as cytomegalovirus, may occasionally be considered. For the many other possible and unusual manifestations of ocular toxoplasmosis, such as pars plani-tis, the differential diagnosis is even broader, and includes autoimmune disorders such as multiple sclerosis and infections such as Lyme...

Clinical Features

They occur 3-8 times the first year, 53 each month, 33 every 2-4 months and 14 more sporadically. The primary episode is the most serious, with erythema, edema and even necrosis. It lasts about 2-6 weeks, and it is accompanied by local and systemic symptoms like headache, malaise and fever. Labial herpes is generally localized at the margin between the skin and mucosa. It predominates on the lips or close to the mouth, but herpetic gingivostomatitis and geometric herpetic glossitis have been described. Genital herpes affects the glans or vulva (Fig. 53.2). Perianal and rectal herpes is seen in homosexuals. It is accompanied by tenesmus and anal discharge and is rarely complicated by urinary retention. Herpetic whitlow in children affects fingers by autoinoculation, almost always arising from an oral infection. In adults, it may be caused by HSV-2, and it follows digital-genital contact. There may be involvement of any part of the body such as cheeks, thighs, and buttocks. Neonatal...

B Dengue Fever Dandy Fever Breakbone Fever

Although arboviruses from mosquitoes, birds, or small rodents are the principal vectors, there are many other viruses that may produce encephalitis. The masslike lesions in the temporal lobes are caused by herpes simplex. The mumps virus, other enteroviruses, or poliovirus can be the cause of encephalitis. It is also produced by the rabies virus.


The two major serotypes of VSV are Indiana and New Jersey. They generally cause nonfatal but economically important disease in cattle, pigs, and horses. The name of the virus comes from the vesicles that it induces on the tongue and lips. Human infection is common in rural areas where VSV is endemic in domestic animals 25-90 of farmers in such areas may have anti-VSV antibodies, showing past infection by the virus. Human infection is largely asymptomatic or associated with a mild febrile illness, sometimes accompanied by herpes-like lesions in the mouth or on the lips or nose. The virus can also replicate in mosquitoes and other arthropods, and has been isolated from mosquitoes during VSV epidemics. The epidemiologic importance of mosquitoes or other hematophagous arthropods in transmission of the virus is not clear.

Viral Delivery Systems

Viral vectors are used in the vast majority of gene therapy trials owing to their relatively high gene transfer efficiency. They may be either RNA or DNA virus based. The DNA viruses include adenovirus, vaccinia, and herpes simplex viruses. The RNA viruses include retroviruses and lentiviruses. To improve their safety, viral vectors may be designed to be replication-deficient, with no further virus particles generated following infection of the target cells. Alternatively, they may be replication-competent or replication-attenuated, in which case viral replication can occur in permissive cells. Vaccinia and Herpes Viruses The main advantages of herpes viruses are their large insert size of 35kb and their ability to infect dividing and nondividing cells. However, they are limited by their potential pathogenicity, poor transduction efficiency, and transient gene expression.

HLA Associations with Ocular Infections

While infections are clearly due to exogenous agents and therefore an environmental factor par excellence for ocular inflammatory disease, it is similarly clear that the host response is critical in determining disease outcome. An elegant animal model of herpes simplex virus (HSV) stromal keratitis that illustrates this, as well as the complexities of HLA in disease, has been reviewed elsewhere 16 . An HSV coat protein, UL-6, shares a seven amino acid sequence with IgG2a. Mice were protected from stromal keratitis if they had a certain IgG2a al-lele, IgG2a b. When mice were infected with HSV, it was thought that a corneal peptide that cross reacted with the specific IgG2a b allele and viral UL-6 was unmasked if mice had the IgG2a b allele they would have developed central tolerance and an immune response was not elicited. Acute retinal necrosis (ARN) is due to infection with either herpes zoster or simplex viruses. As for other manifestations of disease secondary to herpes viruses, it...

Local Delivery Photodynamic Therapy Psoriasis Local Anesthesia and Anti Inflammatory Effect

One of the first suggested applications of iontophoresis was the treatment of herpes labialis and keratitis in surface tissues (82,83) in fact, iontophoresis of idox-uridine has been shown to be effective against herpes simplex viral lesions on the lip. More recently, iontophoresis has also effectively increased acyclovir skin permeation in vitro (67,84). The distribution of this antiviral agent after iontophoresis in human skin in vitro is more homogeneous than that obtained after passive application.

The Many Kinds of Viruses

Three broad classes of viruses can be recognized, which may have independent evolutionary origins. One class, which includes the poxviruses and herpesviruses among many others, contains DNA as the genome, whether single stranded or double stranded, and the DNA genome is replicated by direct DNA DNA copying. During infection, the viral DNA is transcribed by cellular and or viral RNA polymerases, depending on the virus, to produce mRNAs for translation into viral proteins. The DNA genome is replicated by DNA polymerases that can be of viral or cellular origin. Replication of the genomes of most eukaryotic DNA viruses and assembly of progeny viruses occur in the nucleus, but the poxviruses replicate in the cytoplasm.

Virus Receptors and Entry

Cocchi, F., Menotti, L., Mirandola, P. et al. (1998). The ectodomain of a novel member of the immunoglobulin subfamily related to the poliovirus receptor has the attributes of a bona fide receptor for herpes simplex virus types 1 and 2 in human cells. J. Virol. 72 9992-10002.

Epstein Barr viruslinked cancers

Burkitt's lymphoma (BL) is a B cell tumour that occurs with a high frequency in children in central Africa. Shortly after it was first described (by Denis Burkitt) Anthony Epstein established cell lines from the tumour of a patient. The cells were found to be persistently infected with a herpesvirus, which was named Epstein-Barr virus (EBV). Please see Chapter 11 for general characteristics of herpesviruses. Cases of BL also occur in other parts of the world, but generally without an association with EBV. Another tumour that has an association with EBV is nasopharyngeal carcinoma (NPC). This tumour, like BL, is more prevalent in particular regions (Figure 22.4). In both tumours the EBV genome is present in the tumour cells as cccDNA molecules. You will recall that when a herpesvirus infects a cell the linear virus genome becomes circularized (Section 11.5.1).

Neutralization of Charge on the Virion Genome

DNA or RNA has a high net negative charge, and there is a need for counterions to neutralize this charge in order to form a virion. In many viruses, positively charged polymers are incorporated that neutralize half or so of the nucleic acid charge. The DNA in the virions of the polyomaviruses is complexed with cellular histones. The viral genomes in these viruses have been referred to as minichromosomes. In contrast, the adenoviruses encode their own basic proteins that complex with the genome in the core of the virion. Another strategy is used by the herpesviruses, which incorporate polyamines into the virion. Herpes simplex virus has been estimated to incorporate 70,000 molecules of spermi-dine and 40,000 molecules of spermine, which would be sufficient to neutralize about 40 of the DNA charge. Among RNA viruses, the nucleocapsid proteins are often quite basic and neutralize part of the charge on the RNA. As one example, the N-terminal 110 amino acids of the capsid protein of...

Attachment and entry

A virion attaches to receptors on the surface of a potential host cell (Figure 12.6). In the case of B19 virus the host cell is a red blood cell precursor and the receptor is the blood group P antigen. The virion enters the cell by endocytosis and is released from the endosome into the cytoplasm, where it associates with microtubules and is transported to a nuclear pore. With a diameter of 18-26 nm, the parvovirus virion is small enough to pass through a nuclear pore, unlike the herpesvirus nucleocapsid (Section 11.5.1), though there is evidence that the virion must undergo some structural changes before it can be transported into the nucleus. Nuclear localization signals have been found in the capsid proteins of some parvoviruses.

Genome Instability in Transgenic Plants

Acquisition the insect gypsy-like elements (Song et al. 1994), the plant Athila-like elements (Wright and Voytas 1998, 2002), and the Osvaldo element from Drosophila buzzatii (Pantazidis et al. 1999). The nematode Cer elements acquired their env gene from phleboviruses and the Tas element may have acquired it from a Herpesvirus-like ancestor (Malik et al. 2000). LTR-retro-transposons have been found inserted into baculovirus genomes (Malik et al. 2000), e.g. the TED retrotransposon found in the genome of associated Autographa californica nucleopolyhedrosis virus (ACNV) (Friesen and Niessen 1990). Thus, LTR retrotransposons can insert into viral genome, from which it has been suggested they obtained their env gene (Malik et al. 2000).

Lymphocytic Choriomeningitis

HPI A clinical diagnosis of HSV encephalitis had previously been made, for which the patient was treated with two courses of acyclovir without any amelioration of symptoms the disease continued to progress both radiologically and clinically. On serology she tested HTV positive. Stereotactic biopsy sections show abnormal brain with rarefaction, numerous reactive astrocytes, foamy histiocytes, and inflammatory infiltrate around some vessels JC virus in situ hybridization shows many positive nuclei no herpesvirus inclusions seen electron microscopy demonstrates cells with typical papovavirus structures in nuclcus.