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Title 

TMPRSS2 and TMPRSS4 facilitate trypsin-independent spread of influenza virus in Caco-2 cells

 

Caco-2 세포에서의 인플루엔자 바이러스의 트립신-비의존적인 감염을 용이하게 하는 TMPRSS2와 TMPRSS4

Authors 

S BertramI GlowackaP BlazejewskaE SoilleuxP AllenS DanischI SteffenSo Young ChoiYoung Woo ParkH SchneiderK SchughartS Pohlmann

Publisher 

American Society for Microbiology

Issue Date 

2010

Citation 

Journal of Virology, vol. 84, no. 19, pp. 10016-10025

Keywords 

Base SequenceCaco-2 CellsDNA PrimersGene Knockdown TechniquesHemagglutinin Glycoproteins, Influenza VirusHost-Pathogen InteractionsHumansMacrophages, AlveolarMembrane ProteinsOrthomyxoviridaePneumocytesRNA InterferenceRNA, MessengerSerine EndopeptidasesSialic AcidsTrypsinVirus Replication

Abstract 

Proteolysis of influenza virus hemagglutinin by host cell proteases is essential for viral infectivity, but the proteases responsible are not well defined. Recently, we showed that engineered expression of the type II transmembrane serine proteases (TTSPs) TMPRSS2 and TMPRSS4 allows hemagglutinin (HA) cleavage. Here we analyzed whether TMPRSS2 and TMPRSS4 are expressed in influenza virus target cells and support viral spread in the absence of exogenously added protease (trypsin). We found that transient expression of TMPRSS2 and TMPRSS4 resulted in HA cleavage and trypsin-independent viral spread. Endogenous expression of TMPRSS2 and TMPRSS4 in cell lines correlated with the ability to support the spread of influenza virus in the absence of trypsin, indicating that these proteases might activate influenza virus in naturally permissive cells. Indeed, RNA interference (RNAi)-mediated knockdown of both TMPRSS2 and TMPRSS4 in Caco-2 cells, which released fully infectious virus without trypsin treatment, markedly reduced the spread of influenza virus, demonstrating that these proteases were responsible for efficient proteolytic activation of HA in this cell line. Finally, TMPRSS2 was found to be coexpressed with the major receptor determinant of human influenza viruses, 2,6-linked sialic acids, in human alveolar epithelium, indicating that viral target cells in the human respiratory tract express TMPRSS2. Collectively, our results point toward an important role for TMPRSS2 and possibly TMPRSS4 in influenza virus replication and highlight the former protease as a potential therapeutic target.

ISSN 

0022-538X

Link 

http://dx.doi.org/10.1128/JVI.00239-10

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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