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J Virol. PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models.
PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models. (J Virol., abstract, edited)
8. J Virol. 2010 Feb 24. [Epub ahead of print]
PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models.
Hai R, Schmolke M, Varga ZT, Manicassamy B, Wang TT, Belser JA, Pearce MB, Garc?a-Sastre A, Tumpey TM, Palese P. - Department of Microbiology, Institute of Global Health and Emerging Pathogens, Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York; Immunology and Pathogenesis Branch, Influenza Division, CCID, NCIRD, Centers for Disease Control and Prevention, Atlanta, Georgia.
Unlike previous pandemic viruses, the 2009 H1N1 pandemic influenza virus does not code for the virulence factor PB1-F2. The genome of the 2009 H1N1 virus contains three stop codons preventing PB1-F2 expression; however, PB1-F2 production could occur following genetic mutation or reassortment. Thus, it is of great interest to understand the impact that expression of the PB1-F2 protein might have in the context of the 2009 pandemic influenza virus, A/California/04/2009 (Cal/09). We have addressed this question by generating two Cal/09 viruses with productive PB1-F2 open reading frames containing either an asparagine at position 66 of PB1-F2 (66N) or a serine at position 66 (66S): this N66S change has previously been shown to be associated with increased virulence in mice. We used these viruses to investigate the effect on virulence conferred by expression of the 66N or 66S PB1-F2 proteins in both in vitro and in vivo systems. Our results show enhanced replication of the 66S virus in A549 cells, while studies in BALB/c and DBA/2 mice and in ferrets revealed no significant differences in symptoms of infection with the wild-type Cal/09, the 66N or the 66S virus variants. Also co-infection of mice with Streptococcus pneumoniae and the different viruses (rWT Cal/09, 66N and 66S) did not result in significant differences in mortality. Mice infected with either PB1-F2-expressing virus did demonstrate altered protein levels of pro-inflammatory cytokines; differences were observed to be greater in infection caused by the 66S virus. In summary, our study demonstrates that PB1-F2 expression by the Cal/09 virus modulates the immune response to infection while having minimal effect on virus virulence in two mammalian models.
PMID: 20181699 [PubMed - as supplied by publisher]
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8. J Virol. 2010 Feb 24. [Epub ahead of print]
PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models.
Hai R, Schmolke M, Varga ZT, Manicassamy B, Wang TT, Belser JA, Pearce MB, Garc?a-Sastre A, Tumpey TM, Palese P. - Department of Microbiology, Institute of Global Health and Emerging Pathogens, Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York; Immunology and Pathogenesis Branch, Influenza Division, CCID, NCIRD, Centers for Disease Control and Prevention, Atlanta, Georgia.
Unlike previous pandemic viruses, the 2009 H1N1 pandemic influenza virus does not code for the virulence factor PB1-F2. The genome of the 2009 H1N1 virus contains three stop codons preventing PB1-F2 expression; however, PB1-F2 production could occur following genetic mutation or reassortment. Thus, it is of great interest to understand the impact that expression of the PB1-F2 protein might have in the context of the 2009 pandemic influenza virus, A/California/04/2009 (Cal/09). We have addressed this question by generating two Cal/09 viruses with productive PB1-F2 open reading frames containing either an asparagine at position 66 of PB1-F2 (66N) or a serine at position 66 (66S): this N66S change has previously been shown to be associated with increased virulence in mice. We used these viruses to investigate the effect on virulence conferred by expression of the 66N or 66S PB1-F2 proteins in both in vitro and in vivo systems. Our results show enhanced replication of the 66S virus in A549 cells, while studies in BALB/c and DBA/2 mice and in ferrets revealed no significant differences in symptoms of infection with the wild-type Cal/09, the 66N or the 66S virus variants. Also co-infection of mice with Streptococcus pneumoniae and the different viruses (rWT Cal/09, 66N and 66S) did not result in significant differences in mortality. Mice infected with either PB1-F2-expressing virus did demonstrate altered protein levels of pro-inflammatory cytokines; differences were observed to be greater in infection caused by the 66S virus. In summary, our study demonstrates that PB1-F2 expression by the Cal/09 virus modulates the immune response to infection while having minimal effect on virus virulence in two mammalian models.
PMID: 20181699 [PubMed - as supplied by publisher]
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