title: Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium.
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.
authors.affiliation: Institute of Virology, Philipps University, Hans-Meerwein str. 3, 35043 Marburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Böttcher
authors.forename: Tatyana
authors.initials: T
authors.lastname: Matrosovich
authors.forename: Michaela
authors.initials: M
authors.lastname: Beyerle
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Garten
authors.forename: Mikhail
authors.initials: M
authors.lastname: Matrosovich
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D004789:Enzyme Activation; D004848:Epithelium / Q000201:enzymology; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology*; D009975:Orthomyxoviridae / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D006389:Hemagglutinins, Viral; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; C112256:human airway trypsin-like protease