Emergence of Influenza Viruses and Crossing the Species Barrier
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Influenza A virus structure and molecular determinants conferring pathogenesis and host range. Influenza A is an enveloped, negative-sense RNA virus with an eight-segment genome. The virion is studded with surface glycoproteins HA and NA and the M2 ion channel. Pathogenesis and transmission are mediated by multiple genes. Predominant molecular characteristics conferring these traits are diagrammed on each gene product above and as follows. HA: Sialic acid binding restrictions are partially mediated by residues 226 and 228 at the receptor binding site. The presence or absence of a multibasic cleavage site influences the cleavability of the virus by a broader range of enzymes, which leads to high pathogenicity of the virus in host species by causing a systemic infection (13). NA: Sialidase activity is specific to the binding restrictions of the HA protein and cleaves sialic acid residues, permitting release (14); deletions in the stalk region may confer adaptation to domestic poultry (13). PB2: Positions 627 (76) and 701 (22) are associated with enhanced replication in mammals. The immunomodulatory potential of changes or expression of the following proteins may contribute to early and productive replication in a new host. NS1: Position F92E/D confers cytokine resistance in mammalian hosts (77). PB1-F2: Position N66S is associated with increased virulence and cytokine dysregulation in mice (78). PA-X: Expression of this protein may lessen immunopathology during viral infection (3). doi:10.1128/microbiolspec.OH-0010-2012.f1
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Transmission and host range of influenza A viruses. Wild aquatic birds, and possibly bats, serve as the reservoir for influenza A viruses. Well-established transmission events from the reservoir to other host species are represented by solid lines with directionality indicated by arrowheads. Less frequent transmission or events for which data are anecdotal are represented by dotted lines. *bats. Molecular characterization only. doi:10.1128/microbiolspec.OH-0010-2012.f2