Ms2

Figure 19.2 Genetic maps ofssRNA phages MS2 and Q 3. Nucleotide coordinates are shown along the maps. The solid blue boxes are intergenic regions. MS2 genes for maturase (maturation protein) coat (capsid) protein replicase protein for RNA-dependent RNA replication and lysis protein (from overlapping coat and replicase genes). The Min Jou interaction involves nucleotides 1427-1433 and 1738-1744. Qp genes for maturase coat protein replicase protein and read-through protein. The Qp genome is...

K

Figure 2.10 Separation of proteins and estimation of their molecular weights using SDS-PAGE. Lanes 1 and 3 contain standard proteins of known molecular weight. Lane 2 contains the four capsid proteins of a picornavirus. 2.7.2 Detection of infectivity using cell cultures Not all virions have the ability to replicate in host cells. Those virions that do have this ability are said to be 'infective', and the term 'infectivity' is used to denote the capacity of a virus to replicate. Virions may be...

Hiv

Examples of Vertebrate Virus Vectors Figure 4.3 Vectors of vertebrate viruses. Photograph credits mosquito (Aedes aegypti) courtesy of James Gathany and the US Centers for Disease Control and Prevention midge (Culicoides sp.) from Defra website. Crown copyright material, reproduced with the permission of the Controller of HMSO and Queen's Printer for Scotland tick (Ixodes nanus) courtesy Dr. Frantisek Dusbabek, Institute of Parasitology, Academy of Sciences of the Czech Republic become infected...

Jlji

Figure 19.18 Genetic organization in phage lambda. (a) Simplified genetic map (non-integrated). Some of the essential X genes are shown. Gene products functions are as follows A to J, head and tail proteins and assembly stf and tfa, side tail fibres b2 region, non-essential genes, part of the region replaced in X cloning vectors sib, regulatory sequence for int and xis expression - int can be transcribed from Pi and PL. Expression from PL is inhibited when sib is present. PL transcript...

Preface

Virology is a fascinating and rapidly developing subject, and is worthy of study purely because viruses are interesting Furthermore, virology is a branch of science that is of immense relevance to mankind for a host of reasons, not least of which are the threats to human health caused by viruses, such as HIV, hepatitis B virus, papillomaviruses, measles and influenza viruses, to mention just a few. There is a continuing need for trained virologists, and it is hoped that this book will play a...

Introduction to hepadnaviruses

The hepadnaviruses got their name because they cause hepatitis and they have DNA genomes. They are known as hepatitis B viruses (HBVs) and are classified in the family Hepadnaviridae. Some members infect mammals and some infect birds examples include wood-chuck HBV and heron HBV. The best-known hepad-navirus is that which infects humans it is commonly referred to as HBV, and is of major importance as an agent of disease and death. Duck HBV, on the other hand, is non-pathogenic in its natural...

Introduction to retroviruses

The retroviruses are RNA viruses that copy their genomes into DNA during their replication. Until the discovery of these viruses it had been dogma that the transfer of genetic information always occurs in the direction of DNA to RNA, so finding that some viruses carry out 'transcription backwards' (reverse transcription) caused something of a revolution. We now know that reverse transcription is carried out, not only by these RNA viruses, but also by some DNA viruses (see Chapter 18) and by...

Introduction to assembly and exit of virions from cells

In this chapter we deal with the final two stages of our generalized replication cycle assembly of virions and their exit from the cell. There is a requirement for a virion to be a stable structure that will survive in the environment as an infectious entity (though there is huge variation amongst viruses in the degree of stability, as discussed in Chapter 23). There is, however, also a requirement for a virion to become unstable during infection of a host cell so that the viral genome can be...

Overview of virus replication

The aim of a virus is to replicate itself, and in order to achieve this aim it needs to enter a host cell, make copies of itself and get the new copies out of the cell. In general the process of virus replication can be broken down into seven steps 1. Attachment of a virion to a cell 3. Transcription of virus genes into messenger RNA molecules (mRNAs) 4. Translation of virus mRNAs into virus proteins 6. Assembly of proteins and genomes into virions 7. Exit of the virions from the cell. The...

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...

Mechanisms of virus evolution

In many respects, the underlying processes that drive virus evolution are the same as those that drive the evolution of cellular organisms. These processes involve the generation of genome variants, the vast majority of which are deleterious and do not survive, but a few provide an advantage in a particular niche. For a virus the niche might be a new host species or the presence of an antiviral drug, and a variant may proliferate in that niche as a new virus strain. Virus genome variants arise...

R

Figure 16.5 Retrovirus transcription. Genome-Length RNAs are synthesized. Some wiLL function as mRNAs (shown in green) while some will become the genomes of progeny virions (shown in blue). These RNAs are identical they are shown in different colours to emphasize the two functions. Figure 16.5 Retrovirus transcription. Genome-Length RNAs are synthesized. Some wiLL function as mRNAs (shown in green) while some will become the genomes of progeny virions (shown in blue). These RNAs are identical...

The proteinonly hypothesis

If the protein-only hypothesis is correct, and the infectious agent is misfolded prion protein, then transmission of a prion disease implies that the introduction of the misfolded protein into the body of a new host initiates the misfolding of protein molecules in that host. If the agent is 'transmitted' to other species then, because each species makes a specific prion protein, the molecules that become misfolded have the amino acid sequence of the recipient prion, not that of the donor. The...

Genome

Parvoviruses have genomes composed of linear ssDNA in the size range 4-6 kb. At each end of a DNA molecule there are a number of short complementary sequences that can base pair to form a secondary structure (Figure 12.4). Some parvovirus genomes have sequences at their ends known as inverted terminal repeats (ITRs), where the sequence at one end is complementary to, and in the opposite orientation to, the sequence at the other end (Section 3.2.6). As the sequences are complementary, the ends...

Hiv1

Most mutations to drug resistance of HIV-1 are amino acid substitutions, like the examples in Table 25.3, but some mutations are deletions or insertions. Clinical problems arise when drug-resistant virus strains emerge in patients undergoing treatment and when resistant strains are transmitted to other individuals. When such problems arise patients may be treated with alternative drugs. Infections with aciclovir-resistant HSV strains can be treated with foscarnet or cidofovir, neither of which...

Other reversetranscribing DNA viruses

There are some plant viruses with dsDNA genomes that replicate by reverse transcription. These viruses are Figure 18.18 Outline of the HBV replication cycle. Genome replication involves the synthesis of RNA in the nucleus, then copying from RNA to DNA (reverse transcription) in capsids. Stages in virion assembly include capsid construction and acquisition of the envelope by budding. Details of the mode of exit of virions and non-infectious particles from the cell are not shown. classified in...

B

Figure 18.8 PhyLogenetic tree showing relationships between HBV isolates from humans (genotypes A-G) and other primate species. From Kidd-Ljunggren, Miyakawa and Kidd (2002) Journal of General Virology, 83, 1267. Reproduced by permission of the Society for General Microbiology and the authors. Since the publication of this phylogenetic tree a further HBV genotype (H) has been described. Figure 18.9 Attachment of HBV virion to receptor on host cell. The virus attachment site is on the L protein.

Doublestranded RNA replication

Double-stranded RNA, like dsDNA, must be unwound with a helicase in order for the molecule to be replicated. Figure 7.6 Conservative and semi-conservative replication ofdsRNA. Some dsRNA viruses, e.g. Pseudomonas phage 96 (9 Greek letter phi), replicate their genomes by a semi-conservative mechanism, similar to dsDNA replication (Section 7.5) each of the double-stranded progeny molecules is made up of a parental strand and a daughter strand. Other dsRNA viruses, including members of the family...

Rna

Figure 3.9 Heiicai symmetry. (a) Structure of a capsid with helical symmetry. The ssRNA coils are coated with repeated copies of a protein. (b) Part of measles virus nucleocapsid. The complete nucleocapsid is folded and enclosed within an envelope. Reconstructed image from cryo-electron microscopy, courtesy of Dr. David Bhella (MRC Virology Unit, Glasgow). Reinterpretation of data in Bhella et ai. (2004) Journal of Molecular Biology, 340, 319 (by permission of Elsevier Limited). (c) Beet...

At a glance

RNA molecules that existed before cells errors during nucleic acid replication recombination between virus strains reassortment between virus strains acquisition of cell genes. Evolution of viruses can be monitored by sequencing their genomes and creating phylogenetic trees

Books

L., Decman V. and Hendricks R. L. (2005) Neurons and host immunity conspire to maintain herpes simplex virus in a latent state, pp. 203-213 in Molecular Pathogenesis of Virus Infections, editors Digard P., Nash A. A. and Randall R. E., 64th Symposium of the Society for General Microbiology, Cambridge University Press Knipe D. M. and Howley P. M., editors-in-chief (2001) Fields Virology, 4th edition, Chapters 71-83, Lippincott, Williams and Wilkins Sandri-Goldin R. M., editor (2006)...

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-1 commonly infects via the lips or the nose between the ages of 6 and 18 months. A latent infection may be reactivated if, for example, the host becomes stressed or immunosuppressed. Reactivation results in the production of virions, which in...

Info

Figure 2.15 Example of a TCID50 assay. (a) Tenfold dilutions of the virus were inoculated into cell cultures grown in the wells of a plate. Each well received 1 ml virus suspension, except for the control wells, which each received 1 ml diluent. (b) After incubation the cell culture in each well was scored '+' or' ' for CPE. (c) The results of the assay. Dishes are selected that have plaque numbers within a certain range, e.g. 30-300. The plaques are counted and the concentration of virus in...

Assembly and release of virions

Some retroviruses form immature particles in the cytoplasm that are then transported to the plasma membrane, but most retroviruses assemble their components on the inner surface of the plasma membrane (Figure 16.9). The N termini of the Gag and Gag-Pol proteins become anchored to the plasma membrane by the myristyl groups, and the association is stabilized through electrostatic interactions between positive charges in the MA domains and negatively charged phosphate groups in the membrane. The...

L

Derived from cryo-eLectron microscopy images of capsids assembled in E. coli ceLLs expressing HBV C protein. The bar represents 5 nm. From Watts et al. (2002) The EMBO Journal, 21, 876. Reproduced by permission of Nature Publishing Group and the authors. Figure 18.4 HBV capsid. Derived from cryo-eLectron microscopy images of capsids assembled in E. coli ceLLs expressing HBV C protein. The bar represents 5 nm. From Watts et al. (2002) The EMBO Journal, 21, 876. Reproduced...

Aaa

Figure 14.13 Picornavirus transcription and genome replication. The genome acts as a template for synthesis of ( ) RNA and VPg functions as a primer to initiate synthesis. ( ) RNA acts as the template for synthesis of (+) RNA, some of which functions as mRNA, some as progeny genomes and some as templates for further ( ) RNA synthesis. Infected cell cultures develop cytopathic effects for example, Vero cells (a monkey cell line) infected with poliovirus become rounded (Figure 2.11). Lysis of the...

J

Most of the genes are Labelled according to their Location in the genome UL in the unique long region US in the unique short region RL in the repeats flanking the unique long region. Some genes are labelled a or y. This refers to the phase of gene expression (see Section 11.5.2). LAT latency-associated transcript (see Section 11.6). Modified with permission of the authors Gerald Myers and Thomas Brettin, from data on Los Alamos National Laboratory website(http...

Ltr

The tax gene of the provirus is expressed. The Tax protein, compLexed with cell proteins, activates transcription of the provirus and may also activate cell genes. Table 22.2 Examples of retroviral oncogenes and the cell proto-oncogenes from which they were derived. The names of some genes are derived from the virus names. The names of viral oncogenes are prefixed by 'v-', while the names of cell proto-oncogenes are prefixed by 'c-' Table 22.2 Examples of...

Evolution of viruses

' endless forms most beautiful and most wonderful have been, and are being, evolved' Charles Darwin (1859). Charles Darwin's concepts of over-reproduction and survival of the fittest that have been found to apply to cellular organisms also apply to viruses. Like a cellular organism, a virus has genes that strive to perpetuate themselves. The expression of the combination of genes that constitutes the genome permits the virus to replicate itself. Changes to individual genes and new gene...

Virion exit from the infected cell

The virions of many viruses are released from the infected cell when it bursts (lyses), a process that may be initiated by the virus. Many phages produce enzymes (lysins, such as lysozymes) that break bonds in the peptidoglycan of the host bacterial cell walls. Other phages synthesize proteins that inhibit host enzymes with roles in cell wall synthesis this leads to weakening of the cell wall and ultimately to lysis. Average yields of infectious virions per cell (burst sizes Section 2.8.3) vary...

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...

Initiation of genome replication

Each virus genome has a specific sequence where nucleic acid replication is initiated. This sequence is recognized by the proteins that initiate replication. Figure 7.2 3' end of a ssDNA where self-priming of DNA synthesis can occur. Nucleic acid replication requires priming, which is the first reaction of a nucleotide with an -OH group on a molecule at the initiation site. Replication of the genomes of many RNA viruses (including rotaviruses, and rhabdoviruses) initiates when the first...

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...

Screening compounds for antiviral activity

In this approach to the search for clinically useful antiviral drugs, large numbers of compounds are tested for Figure 25.1 Virus activities that are potential drug targets. A generalized view of virus replication is depicted no single virus performs all of these activities DNA replication provides a target if the virus produces enzymes (e.g. DNA polymerase, thymidine kinase) distinct from those of the host. possible anti-viral activity. Some of the compounds chosen in the past had already been...

Transcription

Once the RNA and its associated proteins (N, P and L) are free in the cytoplasm transcription of the virus genome can begin (Figure 15.7). A plus-strand leader RNA, the function of which is uncertain, and five mRNAs are synthesized. Transcription is carried out by an RNA-dependent RNA polymerase activity that resides, along with four Genome organization and gene products

Introduction to rhabdoviruses

The rhabdoviruses have minus-strand RNA genomes in the size range 11-15 kb. The name of these viruses is derived from the Greek word rhabdos, which means a rod. The virions of some rhabdoviruses, especially those infecting plants, are in the shape of rods with rounded ends, while others, especially those infecting animals, are bullet shaped (Figure 15.1). Rhabdoviruses are found in a wide range of hosts, including mammals, fish, plants and insects, and many Courtesy of Thorben Lundsgaard and...

Ill I

Figure 8.1 Assembly of a heiicai nucieocapsid. A few copies of a protein species bind to a helical ssRNA molecule, then more copies bind until the RNA is completely coated. Figure 8.2 Assembly of an icosahedrai nucieocapsid. A protein shell (procapsid) is constructed. A copy of the virus genome enters the procapsid, which undergoes modifications to form the capsid. the icosahedron vertex attached to one end of the connector has five-fold rotational symmetry (Section 3.4.2) the tail attached to...

Sources of further information

Chiu W. et al., editors (1997) Structural Biology of Viruses, Oxford University Press Fischer W. B., editor (2005) Viral Membrane Proteins Structure, Function and Drug Design, Kluwer-Plenum Harrison S. C. (2001) Principles of virus structure. Chapter 3 in Fields Virology, editors-in-chief Knipe D. M. and How-ley P. M., 4th edition, Lippincott, Williams and Wilkins Caspar D. L. D. and Klug A. (1962) Physical principles in the construction of regular viruses Cold Spring Harbor Symposia...

Epstein Barr virus

Epstein-Barr virus (EBV) is transmitted in saliva. Epithelial cells are infected first then the infection spreads to B cells, which are the main host cell type for this virus. More than 90 per cent of people become infected with EBV, usually during the first years of life, when infection results in few or no symptoms. In developed countries some individuals do not become infected until adolescence or adulthood. A proportion of these individuals develop infectious mononucleosis (glandular...

N

Figure 5.1 Ceii receptors with immunogiobuiin-iike domains. Each Loop indicates an immunogLobuLin-Like domain. Most of the domains are stabilized by one or two disuLphide (-S-S-) bonds. In each receptor the virus binding site is Located in the outermost domain. No covalent bonds are formed between virions and receptors. Initially, a virion is weakly bound to a cell at only one or a few receptors. At this stage the attachment is reversible and the virion may detach, but if it remains attached...

International Committee on Taxonomy of Viruses

By 1966 it was decided that some order had to be brought to the business of naming viruses and classifying them into groups, and the International Committee on Taxonomy of Viruses (ICTV) was formed. The committee now has many working groups and is advised by virologists around the world. The ICTV lays down the rules for the nomenclature and classification of viruses, and it considers proposals for new taxonomic groups and virus names. Those that are approved are published in book form (Please...

V

Figure 6.1 Transcription of virus genomes. (+) RNA and (+) DNA have the same sequence as the mRNA (except that in DNA thymine replaces uracil). ( ) RNA and ( ) DNA have the sequence complementary to the mRNA (except that in DNA thymine replaces uracil). (+) and ( ) strands are not indicated for the dsDNA of the Class I viruses as the genomes of most of these viruses have open reading frames (ORFs) in both directions. (+) and ( ) strands are indicated for the ssDNA of the Class II viruses. Most...

Nh

Figure 25.6 Binding of oseltamivir to influenza virus neuraminidase. The inset shows the amino acid residues (one-Letter abbreviations together with their codon numbers) that bind oseltamivir. emerged as a result of natural selection. The fact that viruses, especially RNA viruses, can mutate at high frequencies and evolve rapidly (Section 20.3.3.a) means that genotypes encoding drug resistance can arise rapidly. Drug-resistant genotypes may be at an advantage in hosts where the drug is present...

Transcription and translation

Figure 12.7 Conversion of ssDNA to dsDNA by the ceii DNA polymerase. Not all steps are shown, as indicated by the dashed arrow. The cell RNA polymerase II transcribes the virus genes and cell transcription factors play key roles. The primary transcript(s) undergo various splicing events to produce two size classes of mRNA (Figure 12.8). The larger mRNAs encode the non-structural proteins and the smaller mRNAs encode the structural proteins (see genome organization, Figure 12.5). The...

Early events

The outer layer of the virion is removed, leaving a double-layered particle (Figure 13.1(b)) in which transcription is activated (Figure 13.6). It is likely that each of the 11 genome segments is associated with a molecule of VP1, which synthesizes a new copy of the (+) RNA, and a molecule of VP3, which caps the 5' end of the new RNA. The nucleotides for RNA synthesis enter the particles through the channels in the protein layers and the transcripts are extruded from the particles through the...

DNA vaccines

The most revolutionary approach to vaccination is the introduction into the vaccinee of DNA encoding an antigen, with the aim of inducing cells of the vaccinee to synthesize the antigen. One advantage of this approach is that there is a steady supply of new antigen to stimulate the immune system, as with live virus vaccines. Because the antigen (a virus protein in this case) is produced within the cells of the vaccinee, it is likely to stimulate efficient T-cell-mediated responses. Figure 24.5...

Dna

Figure 14.19 Production of a Picornavirus mutant by reverse genetics. Virus RNA is reverse transcribed to DNA, which is genetically manipulated and cloned in bacterial cells. The DNA is transcribed to RNA, which is transfected into cells. Virus replication in the cells leads to the production of mutant virus. report of the production of infectious virus outside cells. Cell-free systems based on cytoplasmic extracts have subsequently been used to investigate features of the poliovirus...

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...

Origins of viruses

Viruses by definition are parasites of cells, so there could be no viruses until cells had evolved. There is evidence for the presence of living cells about 3.9 billion years ago (Figure 20.1), though the first cells probably came into existence several hundred million years earlier. It is believed that, prior to the development of these primitive prokaryotes, there was a phase of evolution involving organic molecules. These molecules probably included proteins and RNA molecules, and some of...

Paramyxoviruses 2122a Hendra virus

In 1994 at Hendra in south-east Australia there was an outbreak of pneumonia in horses, then a trainer and a stable hand who worked with the horses developed severe respiratory disease. The horses and the two humans were found to be infected with a virus that had characteristics of the family Paramyxoviridae (Figure 21.2). This family contains well known viruses such as measles and mumps viruses, but the virus that was isolated was previously unknown. Thirteen of the horses and the trainer died...

Synthetic peptide vaccines

Each protein antigen has one or more epitopes. These short amino acid sequences can be synthesized in a machine and it was suggested that the resulting peptides might be used as vaccines. Compared with traditional vaccines it would be easier to ensure the absence of contaminants such as viruses and proteins. A lot of work has been done to try to develop peptide vaccines against foot and mouth disease virus. In this virus there is an important epitope within the virion protein VP1 (Section...

New strains of influenza virus A

The family Orthomyxoviridae includes the influenza A viruses (Figure 3.20). The virions have two species of surface glycoprotein a haemagglutinin (H) and a neuraminidase (N). There are 16 types of H antigen and nine types of N antigen, and there are many subtypes of each type. From time to time a virus emerges with a new combination of H and N genes formed by reassortment, and causes a pandemic (see Chapter 20). The hosts of influenza A viruses are principally birds that frequent aquatic...

Storage and transport of vaccines

Once a vaccine has been manufactured there is a need to preserve its efficacy until it is used. For live vaccines this means preserving virus infectivity for vaccines containing inactivated virions, subunits and virus-like particles it means preserving immunogenicity. The major physical and chemical factors that can reduce the infectivity of a live vaccine were considered in Chapter 23 some of these factors can also reduce the immunogenicity of vaccines. Most vaccines are stored and transported...

Transmission of plant viruses

Plant cells are surrounded by thick cell walls that present significant barriers to virus entry most plant viruses are carried across these barriers by vectors. A wide variety of organisms use plants as sources of nutrition and some of these organisms, especially invertebrates, act as virus vectors (Figure 4.2). Many fat b dy blood meal surrounded fat b dy blood meal surrounded Figure 4.1 Cross-section of a mosquito. Some of the organs and tissues that may become infected by a virus acquired in...

Singlestranded DNA to doublestranded DNA

In the nucleus the single-stranded virus genome is converted to dsDNA by a cell DNA polymerase (Figure 12.7). The ends of the genome are double stranded as a result of base pairing (Figure 12.4), and at the 3' end the -OH group acts as a primer to which the enzyme binds. Figure 12.6 Parvovirus attachment and entry. A virion is taken into the cell by endocytosis. After release from the endosome it is transported on a microtubule to a site close to the nucleus. It is likely that the virion enters...

Sxd

Figure 22.4 Incidence rates of nasopharyngeal carcinoma in mates. The data (age standardized incidence rates per 100 000) were published by Busson et at. (2004) Trends in Microbiology, 12, 356. The map was drawn by V. Gaborieau and M. Corbex (Genetic Epidemiology Unit, International Agency for Research on Cancer). Reproduced by permission of Elsevier Limited and the authors. A number of other cancers have been found to have associations with EBV, including some cases of Hodgkin's lymphoma...

1

Figure 17.8 HIV-1 Tat and Rev proteins. Features of the proteins and their binding sites in the virus RNA are indicated. The TAR and RRE regions of the RNA have complex secondary structures. The RRE is present in genome-Length RNA and the singly spliced RNAs, but it is absent from the multiply spliced RNAs. genome-length RNA n my * Figure 17.9 HIV-1 late gene expression. Vpu and Env are translated from singly spliced RNAs in the rough endoplasmic reticulum. The inset shows translation of Vpu...

Virus structure

Main types of virion structure Genomes Virology Principles and Applications John B. Carter and Venetia A. Saunders 2007 John Wiley & Sons, Ltd ISBNs 978-0-470-02386-0 (HB) 978-0-470-02387-7 (PB) 3.1 Introduction to virus structure Outside their host cells, viruses survive as virus particles, also known as virions. The virion is a gene delivery system it contains the virus genome, and its functions are to protect the genome and to aid its entry into a host cell, where it can be replicated and...

Other plusstrand RNA viruses

The genomes of plus-strand RNA viruses are translated in the infected cell prior to their transcription. Because the ribosomes in eukaryotic cells usually terminate after translation of the first ORF, the viruses need strategies to ensure that all the proteins encoded in the infecting genome are translated. One strategy is that described above for the picornaviruses. Polyprotein. All the genetic information is encoded in one ORF this is translated to produce a polyprotein which is cleaved to...

Transcription and translation in bacteria

This section starts with a brief summary of transcription from prokaryotic genes. There is one type of DNA-dependent RNA polymerase for transcription in prokaryotes, and the E. coli holoenzyme comprises the catalytic core enzyme containing one P, one P' and two a subunits, and a regulatory protein, the sigma (a) factor. The a factor determines promoter specificity, enabling the polymerase to recognize and bind to specific promoters in the correct orientation to initiate transcription. Bacterial...

Innate immunity in vertebrates

Some aspects of innate immunity that viruses might encounter prior to infecting cells were discussed in Section 4.3.3. Further components of innate immunity that might be encountered after cells have become infected are interferons and natural killer (NK) cells. Interferons are proteins synthesized and secreted by cells in response to virus infection. A potent trigger for interferon production is dsRNA, which is produced, not only by dsRNA viruses, but also by ssRNA viruses as they replicate....

Locations of virus genome replication in eukaryotic cells

As we saw in Chapter 5, when viruses infect eukaryotic cells the genomes of some are delivered to the cytoplasm and some are conveyed to the nucleus. The destination of a virus genome, and hence the location in which it is replicated, varies with the type of genome (Table 7.1). The genomes of most DNA viruses are replicated in the nucleus, but those of some dsDNA viruses are replicated in the cytoplasm. The genomes of most RNA viruses are replicated in the cytoplasm, but those of the...

Introduction to virus transmission

A minimum proportion of the virions produced in infected hosts must be transmitted to new hosts in which more virions can be manufactured. If this does not happen the virus will die out. The only other possibility for the survival of virus genes is for them to be maintained in cells as nucleic acids, which are replicated and passed on to daughter cells when the cells divide. Viruses of bacteria and other microbial hosts are released from infected cells into the environment of the host, where...

Autonomous parvoviruses

A parvovirus that does not require a helper virus was discovered in serum from a healthy blood donor. The virus, named after a batch of blood labelled B19, infects red blood cell precursors. Many infections with B19 are without signs or symptoms, but some result in disease, such as fifth disease (erythema infectiosum), in which affected children develop a 'slapped-cheek' appearance (Figure 12.2). Other diseases caused by B19 virus include aplastic anaemia in persons with chronic haemolytic...

Papillomaviruslinked cancers

Cervical carcinoma is the third most common cancer in women, with approximately half a million new cases and 280 000 deaths in the world each year. Most, if not all, of these cancers result from infection with a papillomavirus. The papillomaviruses are small DNA viruses of mammals and birds (Figure 22.2). There are well over 100 human papillomavirus (HPV) types, differentiated by their DNA sequences. They enter the body through small abrasions and infect keratin-making cells (ker-atinocytes) in...

Books immune responses to virus infections

E., editors (2005) Molecular Pathogenesis of Virus Infections, 64th Symposium of the Society for General Microbiology, Cambridge University Press Chen Y.-B., Fannjang Y. and Hardwick J. M. (2004) Cell death in viral infections, Chapter 17 in When Cells Die II, editors Lockshin R. A. and Zakeri Z., Wiley Whitton J. L. and Oldstone M. B. A. (2001) The immune response to viruses, Chapter 11 in Knipe D. M. and How-ley P. M., editors-in-chief, Fields Virology,...

Adaptive immunity in vertebrates

An important outcome of virus infection in a vertebrate host is the development of a virus-specific immune response triggered by the virus antigens. Regions of antigens known as epitopes bind to specific receptors on lymphocytes, activating cascades of events that result in the immune response. Lymphocytes are the key cells in specific immune responses. There are two classes of lymphocyte B lymphocytes (B cells), which develop in the Bursa of Fabricius in birds and in the bone marrow in...

Introduction to parvoviruses

Parvoviruses are amongst the smallest known viruses, with virions in the range 18-26 nm in diameter. They derive their name from the Latin parvus ( small). The family Parvoviridae has been divided into two subfamilies the Parvovirinae (vertebrate viruses) and the Densovirinae (invertebrate viruses). Some of the genera and species of the two subfamilies are shown in Table 12.1. The subfamily Parvovirinae includes the genus Dependovirus, the members of which are defective, normally replicating...

Latent herpesvirus infection

When infection of a cell with a herpesvirus results in latency rather than a productive infection, multiple Figure 11.10 Formation of a concatemer. See Figure 7.5 for earlier stages of rolling circle replication of DNA. Colour coding indicates the fates of the two parental strands of DNA.

Introduction to virus vaccines

The term vaccination is derived from the Latin word vacca, meaning cow. This is because the original procedure involved the inoculation of material from cowpox lesions into healthy people. Edward Jenner tried the procedure first in 1796 after he noticed that the faces of most milkmaids were unmarked by pocks this was because milkmaids rarely contracted smallpox. They did, however, commonly contract cowpox, so Jenner inoculated material from a milkmaid's cowpox lesion into the arm of an...

F 9f

Escherichia coli cell with phage T4 attached 5 Virology Principles and Applications John B. Carter and Venetia A. Saunders 2007 John Wiley & Sons, Ltd ISBNs 978-0-470-02386-0 (HB) 978-0-470-02387-7 (PB) Viruses are parasites they depend on cells for molecular building blocks, machinery and energy. Virus particles are small dimensions range from approx. 20-400 nm. A virus genome is composed of one of the following Photographs reproduced with permission of 2Animal Sciences Group, Wageningen...

Mass production of viruses for vaccines

The production of the types of vaccine discussed so far (live attenuated, inactivated, subunit and live recombinant) requires large quantities of virions for most viruses these are produced in cell cultures. John Enders demonstrated in 1949 that poliovirus can be grown in primary monkey cell culture and this led to procedures for the mass production of poliovirus for the Salk and Sabin vaccines. It was subsequently found that some monkey cell cultures used for vaccine production had been...

Live recombinant virus vaccines

Recombinant Vaccine Influenza Virus

A recombinant vaccinia virus engineered to contain the gene for the rabies virus G protein has been used to vaccinate wild mammals against rabies. The use of this vaccine was discussed in Section 15.2.1. Figure 24.3 Outline of production method for influenza virus subunit vaccine. Haemagglutinin (H) and neuraminidase (N) are extracted from inactivated influenza virions and purified by sucrose gradient centrifugation. The bands from the gradient are harvested and incorporated into the vaccine.

Live attenuated virus vaccines

A live attenuated vaccine contains a mutant strain of a virus that has been derived from a wild-type virulent strain. Vaccines of this type have a number of advantages over most other types of vaccine. One advantage is that there are increasing amounts of virus antigen in the body as the virus replicates. Another is that a wide-ranging immune response is induced that involves B cells, CD4 T cells and CD8 T cells. There are two properties that the vaccine virus must possess. First, its antigens...

The nature of prions

There is no evidence that the infectious agents that cause TSEs contain any nucleic acid the agents appear to be misfolded forms of normal cell proteins. This 'protein-only' hypothesis was proposed by Stanley Figure 26.1 Brain section from a sheep with scrapie. The spongiform appearance (holes in the tissue) is evident. Magnification x 500. Courtesy of Dr. R. Higgins, University of California, Davis. Figure 26.1 Brain section from a sheep with scrapie. The spongiform appearance (holes in the...

Virion subunit vaccines

A subunit vaccine contains purified components of virions. In the case of influenza the vaccines contain the haemagglutinin (H) and neuraminidase (N) surface glycoproteins. A typical production method is outlined in Figure 24.3. The infectivity of a batch of influenza virions is inactivated with formaldehyde or P-propiolactone, then the virion envelopes are removed with a detergent, such as Triton X-100. This releases the glycoproteins, which form aggregates of H 'cartwheels' and N 'rosettes'....

New viruses 2151 SARS coronavirus

In 2002 a new human respiratory disease emerged in southern China. The following year one of the doctors who had been treating patients travelled to Hong Kong, where he became ill and died. Subsequently, people who had stayed in the same hotel as the doctor travelled to Singapore, Vietnam, Canada and the US, taking the infectious agent with them. The epidemic of severe acute respiratory syndrome (SARS) was under way. The signs and symptoms of SARS resemble those of influenza and include fever,...

How do viruses cause cancer

Most virus-induced cancers develop after a long period of persistent infection with an oncogenic virus for adult T cell leukaemia this period is exceptionally long (around 60 years). The virus infections persist in their hosts in spite of immune responses, such as the production of virus-specific antibodies. Some persistent infections are latent for much of the time (e.g. EBV and KSHV), with only small numbers of virus genes expressed. Others, including HBV and HCV infections, are productive....

Picornavirus Virion

Picornaviruses are small RNA viruses of relatively simple structure Figure 14.4 . The RNA is enclosed by a capsid, which is roughly spherical and has a diameter of about 25-30 nm. The picornavirus capsid has icosahedral symmetry and is made from 60 copies each of four virus proteins a Virion components b Electron micrograph of negatively stained virions of poliovirus Figure 14.4 The picornavirus virion. VPg virus protein, genome Linked. Electron micrograph courtesy of J. Esposito US Centers for...

Methods used in virology

Animal virus plaques in a cell culture 1 Animal virus plaques in a cell culture 1 Phage plaques in a lawn of bacterial cells 2 Phage plaques in a lawn of bacterial cells 2 Separation of virus particles in a density gradient 3 Separation of virus particles in a density gradient 3 Virus-infected cells detected using a virus-specific antibody labelled with a fluorescent dye 4 Virus-infected cells detected using a virus-specific antibody labelled with a fluorescent dye 4 An endosome labelled red...

Coevolution of viruses and their hosts

A virus-host association that has existed for a long period is likely to have evolved a relationship in which the host suffers little or no harm. Examples of such viruses are the dependoviruses Chapter 12 , and some reoviruses, which acquired the 'o' in their name because they were found to be 'orphan' viruses not associated with any disease Chapter 13 . The members of these virus groups that infect Homo sapiens have probably been with us since we diverged as a separate species. When a virus...