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J Virol. 2015 Jan 28. pii: JVI.03194-14. [Epub ahead of print]
The Avian-Origin PB1 Gene Segment Facilitated Replication and Transmissibility of the H3N2/1968 Pandemic Influenza Virus.
Wendel I1, Rubbenstroth D2, Doedt J1, Kochs G2, Wilhelm J3, Staeheli P2, Klenk HD1, Matrosovich M4.
Author information
Abstract
The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape pre-existing immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y.Kawaoka, S.Krauss and R.G.Webster, J Virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Substitution of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus in comparison with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely, by enhancing activity of the viral polymerase complex.
IMPORTANCE:
Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses are still poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here we addressed this long-standing question by modeling the emergence of the H3N2/1968 virus from its putative human and avian precursors. We show that the avian PB1 segment increased activity of the viral polymerase and facilitated viral replication. Our results suggest that in addition to acquisition of antigenically novel HA ("antigenic shift") enhanced viral polymerase activity may be required for the emergence of pandemic influenza viruses from their seasonal human precursors.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25631088 [PubMed - as supplied by publisher]
The Avian-Origin PB1 Gene Segment Facilitated Replication and Transmissibility of the H3N2/1968 Pandemic Influenza Virus.
Wendel I1, Rubbenstroth D2, Doedt J1, Kochs G2, Wilhelm J3, Staeheli P2, Klenk HD1, Matrosovich M4.
Author information
Abstract
The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape pre-existing immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y.Kawaoka, S.Krauss and R.G.Webster, J Virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Substitution of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus in comparison with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely, by enhancing activity of the viral polymerase complex.
IMPORTANCE:
Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses are still poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here we addressed this long-standing question by modeling the emergence of the H3N2/1968 virus from its putative human and avian precursors. We show that the avian PB1 segment increased activity of the viral polymerase and facilitated viral replication. Our results suggest that in addition to acquisition of antigenically novel HA ("antigenic shift") enhanced viral polymerase activity may be required for the emergence of pandemic influenza viruses from their seasonal human precursors.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25631088 [PubMed - as supplied by publisher]