Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines
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 bee...
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doaj-4841b54749e4442dbba80f6077e6936f2020-11-24T22:24:05ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-03-01810.3389/fcimb.2018.00091331455Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell LinesHideki Hayashi0Yoshinao Kubo1Mai Izumida2Etsuhisa Takahashi3Hiroshi Kido4Ko Sato5Mutsuo Yamaya6Hidekazu Nishimura7Kou Nakayama8Toshifumi Matsuyama9Medical University Research Administrator, Nagasaki University School of Medicine, Nagasaki, JapanProgram for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, JapanDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, JapanDivision of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima, JapanDivision of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima, JapanVirus Research Center, Clinical Research Division, Sendai Medical Center, Sendai, JapanDepartment of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai, JapanVirus Research Center, Clinical Research Division, Sendai Medical Center, Sendai, JapanMedical University Research Administrator, Nagasaki University School of Medicine, Nagasaki, JapanDepartment of Cancer Stem Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, JapanCleavage 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.http://journal.frontiersin.org/article/10.3389/fcimb.2018.00091/fullenterokinaseinfluenza A virushemagglutinin processingtransmembrane serine proteasegenome structure and function |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hideki Hayashi Yoshinao Kubo Mai Izumida Etsuhisa Takahashi Hiroshi Kido Ko Sato Mutsuo Yamaya Hidekazu Nishimura Kou Nakayama Toshifumi Matsuyama |
spellingShingle |
Hideki Hayashi Yoshinao Kubo Mai Izumida Etsuhisa Takahashi Hiroshi Kido Ko Sato Mutsuo Yamaya Hidekazu Nishimura Kou Nakayama Toshifumi Matsuyama Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines Frontiers in Cellular and Infection Microbiology enterokinase influenza A virus hemagglutinin processing transmembrane serine protease genome structure and function |
author_facet |
Hideki Hayashi Yoshinao Kubo Mai Izumida Etsuhisa Takahashi Hiroshi Kido Ko Sato Mutsuo Yamaya Hidekazu Nishimura Kou Nakayama Toshifumi Matsuyama |
author_sort |
Hideki Hayashi |
title |
Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines |
title_short |
Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines |
title_full |
Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines |
title_fullStr |
Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines |
title_full_unstemmed |
Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines |
title_sort |
enterokinase enhances influenza a virus infection by activating trypsinogen in human cell lines |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2018-03-01 |
description |
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. |
topic |
enterokinase influenza A virus hemagglutinin processing transmembrane serine protease genome structure and function |
url |
http://journal.frontiersin.org/article/10.3389/fcimb.2018.00091/full |
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