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Emergence of Influenza Viruses and Crossing the Species Barrier

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  • Authors: Zeynep A. Koçer1, Jeremy C. Jones2, and Robert G. Webster3
  • Editors: R. M. Atlas4, S Maloy5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Infectious Diseases, Division of Virology, St. Jude Children’s Research Hospital, Memphis, TN 38105; 2: Department of Infectious Diseases, Division of Virology, St. Jude Children’s Research Hospital, Memphis, TN 38105; 3: Department of Infectious Diseases, Division of Virology, St. Jude Children’s Research Hospital, Memphis, TN 38105; 4: University of Louisville, Louisville, KY; 5: San Diego State University, San Diego, CA;
  • Received 01 November 2012 Accepted 09 December 2012 Published 20 December 2013
  • Robert G. Webster, robert.webster@stjude.org
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  • Abstract:

    Influenza A viruses are zoonotic pathogens that infect a variety of host species including wild aquatic birds, domestic poultry, and a limited number of mammals including humans. The error-prone nature of the virus's replication machinery and its ability to transmit among multiple hosts lead to generation of novel virus variants with altered pathogenicity and virulence. Spatial, molecular, and physiological barriers inhibit cross-species infections, particularly in the case of human infection with avian viruses. Pigs are proposed as a mixing vessel that facilitates movement of avian viruses from the wild bird reservoir into humans. However, the past decade has witnessed the emergence of highly pathogenic and virulent avian H5 and H7 viruses that have breached these barriers, bypassed the pig intermediate host, and infected humans with a high mortality rate, but have not established human-to-human transmissible lineages. Because influenza viruses pose a significant risk to both human and animal health, it is becoming increasingly important to attempt to predict their identities and pathogenic potential before their widespread emergence. Surveillance of the wild bird reservoir, molecular characterization and documentation of currently circulating viruses in humans and animals, and a comprehensive risk assessment analysis of individual isolates should remain a high priority. Such efforts are critical to the pursuit of prevention and control strategies, including vaccine development and assessment of antiviral susceptibility, that will have a direct impact on the well-being of humans and animals worldwide.

  • Citation: Koçer Z, Jones J, Webster R. 2013. Emergence of Influenza Viruses and Crossing the Species Barrier. Microbiol Spectrum 1(2):OH-0010-2012. doi:10.1128/microbiolspec.OH-0010-2012.

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FIGURE 1

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

Citation: Koçer Z, Jones J, Webster R. 2013. Emergence of Influenza Viruses and Crossing the Species Barrier. Microbiol Spectrum 1(2):OH-0010-2012. doi:10.1128/microbiolspec.OH-0010-2012.
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Image of FIGURE 2

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FIGURE 2

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

Citation: Koçer Z, Jones J, Webster R. 2013. Emergence of Influenza Viruses and Crossing the Species Barrier. Microbiol Spectrum 1(2):OH-0010-2012. doi:10.1128/microbiolspec.OH-0010-2012.
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