Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium.
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.
Böttcher
Eva
E
Institute of Virology, Philipps University, Hans-Meerwein str. 3, 35043 Marburg, Germany.
Matrosovich
Tatyana
T
Beyerle
Michaela
M
Klenk
Hans-Dieter
HD
Garten
Wolfgang
W
Matrosovich
Mikhail
M
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*
D006389:Hemagglutinins, Viral; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; C112256:human airway trypsin-like protease