The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases.
Bottom Line: In this study, we investigated an additional trypsin-like protease, TMPRSS4.Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virus in vivo Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality.Here we show that deletion of two host protease genes,Tmprss2 and Tmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection.
Affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research, and University of Veterinary Medicine Hannover, Braunschweig, Germany.Show MeSH
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Mentions: Furthermore, we measured the protein levels of inflammatory chemokines and cytokines in BAL fluid. Three days after infection, increases of the levels of 13 chemokines were observed in C57BL/6 mice compared to mock-infected mice. Most importantly, we observed significantly less expression of IP10, KC, MCP1, MIP1α, RANTES, VEGF, and TNF-α in knockout mice than in wild-type mice (Fig. 5). No detectable levels of IL-1α were observed in knockout samples at this time point.
Affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research, and University of Veterinary Medicine Hannover, Braunschweig, Germany.