Fluav Flubv Flucv Thov

Humans, birds, swine

Humans

Humans

Mammals

Airborne Airborne Airborne Tick-borne

Respiratory disease Respiratory disease Respiratory disease

Worldwide Worldwide Worldwide human pathogen because it causes very large, recurrent epidemics with significant mortality, Influenza A has therefore been the most intensively studied and has been the focus of efforts to control influenza in humans,

Proteins Encoded by the Influenza Viruses

The proteins encoded in the different gene segments of influenza A and influenza C viruses are described in Table 4,8, Influenza A produces 10 proteins from its eight genome segments, and most of these proteins have analogues in other (-)RNA viruses (Fig, 4,1), The matrix protein, M1, and the nucleocapsid protein, NP, perform functions similar to those of M (when present) and N of other (-)RNA viruses, The three proteins encoded in the three largest segments of influenza, called PB2, PB1, and PA (B or A refers to a basic or acidic pK), possess the RNA polymerase activities encoded in the L protein and the P protein of other (-)RNA viruses, Influenza A and B have two surface glycoproteins, called HA and NA, but influenza C has only one, called HEF, These glycoproteins have the receptor binding, fusion, and receptor-destroying activities present in surface glycoproteins of (-)RNA viruses,

Two proteins, called NS1 and NS2 (NS for nonstructural), are produced from RNA segment 8, NS1 is produced from the unspliced mRNA (replication occurs in the nucleus), It binds to RNAs in the nucleus, including cellular pre-mRNAs, cellular snRNAs which are involved in splic ing, and dsRNA, Its activities inhibit the transport of cellular mRNAs from the nucleus and promote the synthesis of influenza mRNA, NS1 also regulates splicing of influenza mRNAs and their transport from the nucleus to the cytosol, Another function of NS1 is to interfere with the interferon pathway (Chapter 8), perhaps by binding dsRNA, Influenza virus lacking NS1 is very sensitive to interferon, whereas the wild-type virus is resistant, NS2 is produced from a spliced mRNA, It interacts with M1 attached to influenza RNP and promotes the transport of the RNP to the cytoplasm, It is present in small quantities in the virion and so is not truly nonstructural,

Protein M2 is produced from a spliced mRNA from segment 7, It forms ion channels in membranes, probably as a tetramer, that allow passage of H+ ions, During transport of HA to the cell surface, the presence of M2 in the membrane of the transport vesicle causes the pH within the vesicle to equilibrate with that in the cytosol, This prevents low pH activation of the fusion activity of HA during transport, because transport vesicles are otherwise acidic, M2 is also present in virions and is required for the disassembly of the virus and for the activation of the RNA polymerase activity, To become active, the poly-merase in the interior of the virus must be exposed to low pH, Influenza virus enters the cell in endosomes, which are progressively acidified, The acidic pH not only triggers a conformational change in HA that results in fusion of the viral membrane with the endosomal membrane, but

TABLE 4.8 Genome Segments of Influenza Viruses

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