Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium
- PMID: 16973594
- PMCID: PMC1617224
- DOI: 10.1128/JVI.01118-06
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.
Figures
Similar articles
-
TMPRSS2 Activates Hemagglutinin-Esterase Glycoprotein of Influenza C Virus.J Virol. 2021 Oct 13;95(21):e0129621. doi: 10.1128/JVI.01296-21. Epub 2021 Aug 18. J Virol. 2021. PMID: 34406864 Free PMC article.
-
Activation of influenza viruses by proteases from host cells and bacteria in the human airway epithelium.Pathog Dis. 2013 Nov;69(2):87-100. doi: 10.1111/2049-632X.12053. Epub 2013 Jul 2. Pathog Dis. 2013. PMID: 23821437 Free PMC article. Review.
-
Novel insights into proteolytic cleavage of influenza virus hemagglutinin.Rev Med Virol. 2010 Sep;20(5):298-310. doi: 10.1002/rmv.657. Rev Med Virol. 2010. PMID: 20629046 Free PMC article. Review.
-
Cleavage of influenza virus hemagglutinin by airway proteases TMPRSS2 and HAT differs in subcellular localization and susceptibility to protease inhibitors.J Virol. 2010 Jun;84(11):5605-14. doi: 10.1128/JVI.00140-10. Epub 2010 Mar 17. J Virol. 2010. PMID: 20237084 Free PMC article.
-
MDCK cells that express proteases TMPRSS2 and HAT provide a cell system to propagate influenza viruses in the absence of trypsin and to study cleavage of HA and its inhibition.Vaccine. 2009 Oct 23;27(45):6324-9. doi: 10.1016/j.vaccine.2009.03.029. Vaccine. 2009. PMID: 19840668
Cited by
-
A Chymotrypsin-Dependent Live-Attenuated Influenza Vaccine Provides Protective Immunity against Homologous and Heterologous Viruses.Vaccines (Basel). 2024 May 8;12(5):512. doi: 10.3390/vaccines12050512. Vaccines (Basel). 2024. PMID: 38793763 Free PMC article.
-
Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19.J Virol. 2024 May 14;98(5):e0190323. doi: 10.1128/jvi.01903-23. Epub 2024 Apr 9. J Virol. 2024. PMID: 38593045
-
Restriction of Viral Glycoprotein Maturation by Cellular Protease Inhibitors.Viruses. 2024 Feb 22;16(3):332. doi: 10.3390/v16030332. Viruses. 2024. PMID: 38543698 Free PMC article. Review.
-
High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains.bioRxiv [Preprint]. 2024 Mar 9:2024.03.08.584176. doi: 10.1101/2024.03.08.584176. bioRxiv. 2024. PMID: 38496577 Free PMC article. Preprint.
-
ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells.J Virol. 2024 Apr 16;98(4):e0010224. doi: 10.1128/jvi.00102-24. Epub 2024 Mar 12. J Virol. 2024. PMID: 38470058
References
-
- Afar, D. E., I. Vivanco, R. S. Hubert, J. Kuo, E. Chen, D. C. Saffran, A. B. Raitano, and A. Jakobovits. 2001. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Res. 61:1686-1692. - PubMed
-
- Boycott, R., H. D. Klenk, and M. Ohuchi. 1994. Cell tropism of influenza virus mediated by hemagglutinin activation at the stage of virus entry. Virology 203:313-319. - PubMed
-
- Chen, Y., M. Shiota, M. Ohuchi, T. Towatari, J. Tashiro, M. Murakami, M. Yano, B. Yang, and H. Kido. 2000. Mast cell tryptase from pig lungs triggers infection by pneumotropic Sendai and influenza A viruses. Eur. J. Biochem. 267:3189-3197. - PubMed
-
- Chokki, M., S. Yamamura, H. Eguchi, T. Masegi, H. Horiuchi, H. Tanabe, T. Kamimura, and S. Yasuoka. 2003. Human airway trypsin-like protease increases mucin gene expression in airway epithelial cells. Am. J. Respir. Cell. Mol. Biol. 30:470-478. - PubMed
-
- Donaldson, S. H., A. Hirsh, D. C. Li, G. Holloway, J. Chao, R. G. Boucher, and S. E. Gabriel. 2002. Regulation of the epithelial sodium channel by serine proteases in human airways. J. Biol. Chem. 277:8338-8345. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources