+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Virulence and genetic compatibility of polymerase reassortant viruses derived from the pandemic (H1N1) 2009 influenza virus and circulating influenza A viruses



Virulence and genetic compatibility of polymerase reassortant viruses derived from the pandemic (H1N1) 2009 influenza virus and circulating influenza A viruses



Journal of Virology 85(13): 6275-6286



Gene mutations and reassortment are key mechanisms by which influenza A virus acquires virulence factors. To evaluate the role of the viral polymerase replication machinery in producing virulent pandemic (H1N1) 2009 influenza viruses, we generated various polymerase point mutants (PB2, 627K/701N; PB1, expression of PB1-F2 protein; and PA, 97I) and reassortant viruses with various sources of influenza viruses by reverse genetics. Although the point mutations produced no significant change in pathogenicity, reassortment between the pandemic A/California/04/09 (CA04, H1N1) and current human and animal influenza viruses produced variants possessing a broad spectrum of pathogenicity in the mouse model. Although most polymerase reassortants had attenuated pathogenicity (including those containing seasonal human H3N2 and high-pathogenicity H5N1 virus segments) compared to that of the parental CA04 (H1N1) virus, some recombinants had significantly enhanced virulence. Unexpectedly, one of the five highly virulent reassortants contained a A/Swine/Korea/JNS06/04(H3N2)-like PB2 gene with no known virulence factors; the other four had mammalian-passaged avian-like genes encoding PB2 featuring 627K, PA featuring 97I, or both. Overall, the reassorted polymerase complexes were only moderately compatible for virus rescue, probably because of disrupted molecular interactions involving viral or host proteins. Although we observed close cooperation between PB2 and PB1 from similar virus origins, we found that PA appears to be crucial in maintaining viral gene functions in the context of the CA04 (H1N1) virus. These observations provide helpful insights into the pathogenic potential of reassortant influenza viruses composed of the pandemic (H1N1) 2009 influenza virus and prevailing human or animal influenza viruses that could emerge in the future.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 056876485

Download citation: RISBibTeXText

PMID: 21507962

DOI: 10.1128/jvi.02125-10


Related references

Virulence of pandemic (H1N1) 2009 influenza A polymerase reassortant viruses. Virulence 2(5): 422-426, 2012

Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses. Journal of General Virology 94(Pt 3): 583-592, 2013

Novel reassortant influenza viruses between pandemic (H1N1) 2009 and other influenza viruses pose a risk to public health. Microbial Pathogenesis 89: 62-72, 2015

Modifications in the polymerase genes of a swine-like triple-reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 viruses. Journal of Virology 85(1): 456-469, 2011

Novel triple reassortant H1N2 influenza viruses bearing six internal genes of the pandemic 2009/H1N1 influenza virus were detected in pigs in China. Journal of Clinical Virology 61(4): 529-534, 2014

High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses. Proceedings of the National Academy of Sciences of the United States of America 108(10): 4164-4169, 2011

Reassortment between seasonal H1N1 and pandemic (H1N1) 2009 influenza viruses is restricted by limited compatibility among polymerase subunits. Journal of Virology 85(16): 8449-8452, 2011

North American triple reassortant and Eurasian H1N1 swine influenza viruses do not readily reassort to generate a 2009 pandemic H1N1-like virus. Mbio 5(2): E00919-13, 2014

Evidence of cross-reactive immunity to 2009 pandemic influenza A virus in workers seropositive to swine H1N1 influenza viruses circulating in Italy. Plos one 8(2): E57576, 2013

Reassortment ability of the 2009 pandemic H1N1 influenza virus with circulating human and avian influenza viruses: public health risk implications. Virus Research 175(2): 151-154, 2013

Pathogenesis and transmission of triple-reassortant swine H1N1 influenza viruses isolated before the 2009 H1N1 pandemic. Journal of Virology 85(4): 1563-1572, 2011

The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/33 viruses. Journal of Virology 88(21): 12339-12347, 2014

Genetic analysis of HA gene of pandemic H1N1 2009 influenza viruses circulating in India. Indian Journal of Medical Microbiology 30(3): 346-349, 2013

Reassortant swine influenza viruses isolated in Japan contain genes from pandemic A(H1N1) 2009. Microbiology and Immunology 58(6): 327-341, 2014

Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses. Journal of Virology 91(17):, 2017