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Virulence and genetic compatibility of polymerase reassortant viruses derived from the pandemic (H1N1) 2009 influenza virus and circulating influenza A viruses.
J Virol. 2011 Jul; 85(13):6275-86.JV

Abstract

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.

Authors+Show Affiliations

Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Heungduk-Ku, Cheongju City, 361-763, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21507962

Citation

Song, Min-Suk, et al. "Virulence and Genetic Compatibility of Polymerase Reassortant Viruses Derived From the Pandemic (H1N1) 2009 Influenza Virus and Circulating Influenza a Viruses." Journal of Virology, vol. 85, no. 13, 2011, pp. 6275-86.
Song MS, Pascua PN, Lee JH, et al. Virulence and genetic compatibility of polymerase reassortant viruses derived from the pandemic (H1N1) 2009 influenza virus and circulating influenza A viruses. J Virol. 2011;85(13):6275-86.
Song, M. S., Pascua, P. N., Lee, J. H., Baek, Y. H., Park, K. J., Kwon, H. I., Park, S. J., Kim, C. J., Kim, H., Webby, R. J., Webster, R. G., & Choi, Y. K. (2011). 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), 6275-86. https://doi.org/10.1128/JVI.02125-10
Song MS, et al. Virulence and Genetic Compatibility of Polymerase Reassortant Viruses Derived From the Pandemic (H1N1) 2009 Influenza Virus and Circulating Influenza a Viruses. J Virol. 2011;85(13):6275-86. PubMed PMID: 21507962.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Virulence and genetic compatibility of polymerase reassortant viruses derived from the pandemic (H1N1) 2009 influenza virus and circulating influenza A viruses. AU - Song,Min-Suk, AU - Pascua,Philippe Noriel Q, AU - Lee,Jun Han, AU - Baek,Yun Hee, AU - Park,Kuk Jin, AU - Kwon,Hyeok-il, AU - Park,Su-Jin, AU - Kim,Chul-Joong, AU - Kim,Hyunggee, AU - Webby,Richard J, AU - Webster,Robert G, AU - Choi,Young Ki, Y1 - 2011/04/20/ PY - 2011/4/22/entrez PY - 2011/4/22/pubmed PY - 2011/8/27/medline SP - 6275 EP - 86 JF - Journal of virology JO - J. Virol. VL - 85 IS - 13 N2 - 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. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/21507962/Virulence_and_genetic_compatibility_of_polymerase_reassortant_viruses_derived_from_the_pandemic__H1N1__2009_influenza_virus_and_circulating_influenza_A_viruses_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=21507962 DB - PRIME DP - Unbound Medicine ER -