Proteolytic Activation of Influenza Viruses by Serine Proteases TMPRSS2 and HAT from Human Airway Epithelium

TLDR

The identity of host proteases that cleave influenza hemagglutinin in the human respiratory tract remains unknown. The study cloned the airway‑localized serine proteases TMPRSS2 and HAT into mammalian expression vectors. Co‑expression of TMPRSS2 or HAT with HA in mammalian cells cleaved HA and enabled influenza replication without exogenous trypsin, indicating these proteases likely activate the virus in vivo.

Abstract

Host cell proteases that cleave the hemagglutinin (HA) of influenza viruses in the human respiratory tract are still not identified. Here we cloned two human type II transmembrane serine proteases with known airway localization, TMPRSS2 and HAT, into mammalian expression vector. Cotransfection of mammalian cells with plasmids encoding HA and either protease resulted in HA cleavage in situ. Transient expression of either protease in MDCK cells enabled multicycle replication of influenza viruses in these cells in the absence of exogenous trypsin. These data suggest that TMPRSS2 and HAT are candidates for proteolytic activation of influenza viruses in vivo.