Abstract
Compatibility among the influenza A virus (IAV) ribonucleoprotein (RNP) genes affects viral replication efficiency and can limit the emergence of novel reassortants, including those with potential pandemic risks. In this study, we determined the polymerase activities of 2,451 RNP reassortants among three seasonal and eight enzootic IAVs by using a minigenome assay. Results showed that the 2009 H1N1 RNP are more compatible with the tested enzootic RNP than seasonal H3N2 RNP and that triple reassortment increased such compatibility. The RNP reassortants among 2009 H1N1, canine H3N8, and avian H4N6 IAVs had the highest polymerase activities. Residues in the RNA binding motifs and the contact regions among RNP proteins affected polymerase activities. Our data indicates that compatibility among seasonal and enzootic RNPs are selective, and enzoosis of multiple strains in the animal-human interface can facilitate emergence of an RNP with increased replication efficiency in mammals, including humans.
Highlights
Influenza A viruses (IAVs) are negative-sense, single stranded RNA viruses containing eight gene segments that encode at least 11 proteins
This study presents an evaluation of the compatibility among the RNP genes between human seasonal and enzootic IAVs at the animal-human interface, and to further identify genetic features associated with RNP replication efficiency
We selected human seasonal H1N1 and H3N2 IAVs and eight enzootic viruses, which caused across species spillover cases (Table 1)
Summary
Influenza A viruses (IAVs) are negative-sense, single stranded RNA viruses containing eight gene segments that encode at least 11 proteins. Reassortment facilitated the emergence of at least three of the four documented pandemic IAVs. The 1957 H2N2 pandemic strain was a reassortant containing HA, NA, and polymerase basic 1 (PB1) of avian-origin and the other five genes (polymerase basic protein 2 [PB2], polymerase acidic protein [PA], nucleoprotein [NP], nonstructural [NS], and matrix [M]) genes from human seasonal H1N1 viruses [8]. The 1968 H3N2 pandemic strain had HA and PB1 of avian-origin and the other six genes from human seasonal H2N2 viruses [8,9]. The 2009 H1N1 pandemic virus contains genes of avianorigin (North American-lineage PB2 and PA), human-origin (PB1 from human seasonal H3N2), and swine origin (classic lineage HA and NP and Eurasian lineage NS, NA, and M) [10]. Risk assessment of potential reassortants among epidemic IAVs and enzootic IAVs is considered a key component in pandemic influenza preparedness
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