Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium.
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ABSTRACT:
SUBMITTER: Bottcher E
PROVIDER: S-EPMC1617224 | biostudies-literature | 2006 Oct
REPOSITORIES: biostudies-literature
Publications
Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium.
Böttcher Eva E Matrosovich Tatyana T Beyerle Michaela M Klenk Hans-Dieter HD Garten Wolfgang W Matrosovich Mikhail M
Journal of virology 20061001 19
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 i ...[more]
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Project description:The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract. Similarly, coexpression of ACE2, the SARS-coronavirus receptor, and TMPRSS2 was frequently found in the upper and lower aerodigestive tract, with the exception of the vocal folds, epiglottis and trachea. Finally, activation of influenza virus was conserved between human, avian and porcine TMPRSS2, suggesting that this protease might activate influenza virus in reservoir-, intermediate- and human hosts. In sum, our results show that TMPRSS2 and HAT are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host.
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