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
Related in: MedlinePlus
Mentions: By immunohistochemistry, influenza virus antigen was present in respiratory epithelial cells, with stronger expression in the nucleus than in the cytoplasm. For the wild-type mice at 2 days p.i., multifocally, few type II alveolar epithelial cells and many bronchiolar and bronchial epithelial cells were expressing virus antigen (Fig. 6A and C). At 4 days p.i., more alveolar cells were positive and fewer bronchiolar and bronchial epithelial cells were positive than at 2 days p.i. At 6 days p.i., there were more positive alveolar epithelial cells and comparable numbers of positive bronchiolar and bronchial epithelial cells compared to those at 4 days p.i. (Fig. 6E). For the knockout mice, there were fewer positive cells overall than the case for wild-type mice (Fig. 6B, D, and F). The number of positive alveolar epithelial cells increased from 2 to 6 days p.i., while the number of bronchiolar and bronchial epithelial cells decreased from 2 to 4 and 6 days p.i.
Affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research, and University of Veterinary Medicine Hannover, Braunschweig, Germany.