Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines

Frontiers in Cellular and Infection Microbiology

Yamaya, Mutsuo¹  Matsuyama, Toshifumi²  Izumida, Mai³  Kido, Hiroshi⁴  Takahashi, Etsuhisa⁴  Nakayama, Kou⁵  Hayashi, Hideki⁵  Kubo, Yoshinao⁶  Sato, Ko⁷  Nishimura, Hidekazu⁷ 

[1]Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Japan

[2]Department of Cancer Stem Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Japan

[3]Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Japan

[4]Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Japan

[5]Medical University Research Administrator, Nagasaki University School of Medicine, Japan

[6]Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Japan

[7]Virus Research Center, Clinical Research Division, Sendai Medical Center, Japan

关键词: Enterokinase;    Influenza A virus;    Hemagglutinin processing;    transmembrane serine protease;    genome structure;    function;   

DOI  :  10.3389/fcimb.2018.00091

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

Cleavage and activation of hemagglutinin (HA) by trypsin-like proteases in influenza A virus (IAV) are essential prerequisites for its successful infection and spread. In host cells, some transmembrane serine proteases such as TMPRSS2, TMPRSS4 and HAT, along with plasmin in the bloodstream, have been reported to cleave the HA precursor (HA0) molecule into its active forms, HA1 and HA2. Some trypsinogens can also enhance IAV proliferation in some cell types (e.g., rat cardiomyoblasts). However, the precise activation mechanism for this process is unclear, because the expression level of the physiological activator of the trypsinogens, the TMPRSS15 enterokinase, is expected to be very low in such cells, with the exception of duodenal cells. Here, we show that at least two variant enterokinases are expressed in various human cell lines, including A549 lung-derived cells. The exogenous expression of these enterokinases was able to enhance the proliferation of IAV in 293T human kidney cells, but the proliferation was reduced by knocking down the endogenous enterokinase in A549 cells. The enterokinase was able to enhance HA processing in the cells, which activated trypsinogen in vitro and in the IAV-infected cells also. Therefore, we conclude that enterokinase plays a role in IAV infection and proliferation by activating trypsinogen to process viral HA in human cell lines.

【 授权许可】

CC BY