PB1-F2 modulates early host responses but does not affect the pathogenesis of H1N1 seasonal influenza virus.
In the context of infections with highly pathogenic influenza A viruses, the PB1-F2 protein contributes to virulence and enhances lung inflammation. In contrast, its role in the pathogenesis of seasonal influenza viral strains is less clear, especially in the H1N1 subtype, where strains can have a full-length 87- to 90-amino-acid protein, a truncated 57-amino-acid version, or lack the protein altogether. Toward this, we introduced the full-length 1918 PB1-F2, or prevented PB1-F2 expression, in H1N1 A/USSR/90/77, a seasonal strain that naturally expresses a truncated PB1-F2. All viruses replicated with similar efficiency in ferret or macaque ex vivo lung cultures and elicited similar cytokine mRNA profiles. In contrast, the virus expressing the 1918 PB1-F2 protein caused a delay of proinflammatory responses in ferret blood-derived macrophages, while the PB1-F2 knockout virus resulted in a more rapid response. A similar but less pronounced delay in innate immune activation was also observed in the nasal wash cells of ferrets infected with the 1918 PB1-F2-expressing virus. However, the three viruses did not differ in their virulence or clinical course in ferrets, supporting speculations that PB1-F2 is of limited importance for the pathogenesis of primary viral infection with human seasonal H1N1 viruses.
INRS-Institut Armand-Frappier, University of Quebec, Laval, Quebec, Canada.
Isabelle
I
Meunier
Veronika
V
von Messling
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D005289:Ferrets; D006801:Humans; D066298:In Vitro Techniques; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D016898:Interferon-alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008252:Macaca fascicularis; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; C442816:PB1-F2 protein, Influenza A virus; D014764:Viral Proteins; D037521:Virulence Factors