PB1-F2 Expression by the 2009 Pandemic H1N1 Influenza Virus Has Minimal Impact on Virulence in Animal Models

Rong Hai; Mirco Schmolke; Zsuzsanna T Varga; Balaji Manicassamy; Taia T Wang; Jessica A Belser; Melissa B Pearce; Adolfo García-Sastre; Terrence M Tumpey; Peter Palese

doi:10.1128/JVI.02717-09

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PB1-F2 Expression by the 2009 Pandemic H1N1 Influenza Virus Has Minimal Impact on Virulence in Animal Models

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PB1-F2 Expression by the 2009 Pandemic H1N1 Influenza Virus Has Minimal Impact on Virulence in Animal Models

Rong Hai, Mirco Schmolke, Zsuzsanna T Varga, Balaji Manicassamy, Taia T Wang, Jessica A Belser, Melissa B Pearce, Adolfo García-Sastre, Terrence M Tumpey and Peter Palese

Journal of virology, Vol.84(9), pp.4442-4450

05/2010

DOI: 10.1128/JVI.02717-09

PMCID: PMC2863736

PMID: 20181699

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Abstract

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 the 66S PB1-F2 protein in both in vitro and in vivo systems. Our results show enhanced replication of the 66S virus in A549 cells, while studies of BALB/c and DBA/2 mice and ferrets revealed no significant differences in symptoms of infection with wild-type Cal/09 versus the 66N or 66S virus variant. Also, coinfection of mice with Streptococcus pneumoniae and the different viruses (recombinant wild-type [rWT] Cal/09 and the 66N and 66S viruses) did not result in significant differences in mortality. Mice infected with either PB1-F2-expressing virus did demonstrate altered protein levels of proinflammatory 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 a minimal effect on virus virulence in two mammalian models.

Pathogenesis and Immunity

Details

Title: Subtitle: PB1-F2 Expression by the 2009 Pandemic H1N1 Influenza Virus Has Minimal Impact on Virulence in Animal Models
Creators: Rong Hai - Department of Microbiology
Mirco Schmolke - Department of Microbiology
Zsuzsanna T Varga - Department of Microbiology
Balaji Manicassamy - Department of Microbiology
Taia T Wang - Department of Microbiology
Jessica A Belser - Department of Microbiology
Melissa B Pearce - Department of Microbiology
Adolfo García-Sastre - Department of Microbiology
Terrence M Tumpey - Department of Microbiology
Peter Palese - Department of Microbiology
Resource Type: Journal article
Publication Details: Journal of virology, Vol.84(9), pp.4442-4450
DOI: 10.1128/JVI.02717-09
PMID: 20181699
PMCID: PMC2863736
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology (ASM)
Language: English
Date published: 05/2010
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083272002771

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