Virulence determinants of pandemic influenza viruses

Abstract

Influenza A viruses cause recurrent, seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. The ability of influenza A viruses to adapt to various hosts and undergo reassortment events ensures constant generation of new strains with unpredictable degrees of pathogenicity, transmissibility, and pandemic potential. Currently, the combination of factors that drives the emergence of pandemic influenza is unclear, making it impossible to foresee the details of a future outbreak. Identification and characterization of influenza A virus virulence determinants may provide insight into genotypic signatures of pathogenicity as well as a more thorough understanding of the factors that give rise to pandemics.

Figure 1. Influenza A virus particle.

Three integral membrane proteins, HA, NA, and the M2 ion channel, are inserted into the viral lipid envelope. The M1 matrix protein lies beneath the envelope. The viral genome is composed of eight segments of vRNA, coated with NP to form vRNPs. The viral transcriptase complex, containing PB1, PB2, and PA, is associated with each RNP. Small amounts of NEP, encoded from the NS gene, are found in purified virions.

Figure 2. Origin of 2009 S-OIV.

Reassortment of North American swine H3N2 and H1N2 triple-reassortant viruses (of North American avian, human [H3N2], and classical swine [H1N1] origin) with Eurasian avian-like swine viruses (H1N1) resulted in the 2009 S-OIV pandemic virus. Each gene segment of avian, human, or swine origin corresponds to a characteristic feature on the surface of the schematic viral particle.

Figure 3. Avian versus human influenza virus preference for sialic acid receptor linkages.

(A) Sialic acid α2,6 and α2,3 linkage to a cell surface glycoprotein is bound preferentially by HA of human and avian influenza viruses, respectively. (B) Crucial residues in HA that dictate receptor preference for human or avian influenza viruses.