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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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Autores principales: Hayashi, Hideki, Kubo, Yoshinao, Izumida, Mai, Takahashi, Etsuhisa, Kido, Hiroshi, Sato, Ko, Yamaya, Mutsuo, Nishimura, Hidekazu, Nakayama, Kou, Matsuyama, Toshifumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876233/
https://www.ncbi.nlm.nih.gov/pubmed/29629340
http://dx.doi.org/10.3389/fcimb.2018.00091
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author Hayashi, Hideki
Kubo, Yoshinao
Izumida, Mai
Takahashi, Etsuhisa
Kido, Hiroshi
Sato, Ko
Yamaya, Mutsuo
Nishimura, Hidekazu
Nakayama, Kou
Matsuyama, Toshifumi
author_facet Hayashi, Hideki
Kubo, Yoshinao
Izumida, Mai
Takahashi, Etsuhisa
Kido, Hiroshi
Sato, Ko
Yamaya, Mutsuo
Nishimura, Hidekazu
Nakayama, Kou
Matsuyama, Toshifumi
author_sort Hayashi, Hideki
collection PubMed
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 (HA(0)) molecule into its active forms, HA(1) and HA(2). 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.
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spelling pubmed-58762332018-04-06 Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines Hayashi, Hideki Kubo, Yoshinao Izumida, Mai Takahashi, Etsuhisa Kido, Hiroshi Sato, Ko Yamaya, Mutsuo Nishimura, Hidekazu Nakayama, Kou Matsuyama, Toshifumi Front Cell Infect Microbiol Microbiology 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 (HA(0)) molecule into its active forms, HA(1) and HA(2). 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. Frontiers Media S.A. 2018-03-23 /pmc/articles/PMC5876233/ /pubmed/29629340 http://dx.doi.org/10.3389/fcimb.2018.00091 Text en Copyright © 2018 Hayashi, Kubo, Izumida, Takahashi, Kido, Sato, Yamaya, Nishimura, Nakayama and Matsuyama. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Hayashi, Hideki
Kubo, Yoshinao
Izumida, Mai
Takahashi, Etsuhisa
Kido, Hiroshi
Sato, Ko
Yamaya, Mutsuo
Nishimura, Hidekazu
Nakayama, Kou
Matsuyama, Toshifumi
Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines
title 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_short 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
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876233/
https://www.ncbi.nlm.nih.gov/pubmed/29629340
http://dx.doi.org/10.3389/fcimb.2018.00091
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