The host protease TMPRSS2 plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses.
Identifieur interne : 001A51 ( Main/Exploration ); précédent : 001A50; suivant : 001A52The host protease TMPRSS2 plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses.
Auteurs : Kouji Sakai [Japon] ; Yasushi Ami ; Maino Tahara ; Toru Kubota ; Masaki Anraku ; Masako Abe ; Noriko Nakajima ; Tsuyoshi Sekizuka ; Kazuya Shirato ; Yuriko Suzaki ; Akira Ainai ; Yuichiro Nakatsu ; Kazuhiko Kanou ; Kazuya Nakamura ; Tadaki Suzuki ; Katsuhiro Komase ; Eri Nobusawa ; Katsumi Maenaka ; Makoto Kuroda ; Hideki Hasegawa ; Yoshihiro Kawaoka [États-Unis] ; Masato Tashiro ; Makoto TakedaSource :
- Journal of virology [ 1098-5514 ] ; 2014.
Descripteurs français
- KwdFr :
- Analyse de survie, Animaux, Dose létale 50, Femelle, Glycoprotéine hémagglutinine du virus influenza (métabolisme), Infections à Orthomyxoviridae (anatomopathologie), Infections à Orthomyxoviridae (virologie), Interactions hôte-pathogène, Modèles animaux de maladie humaine, Poumon (virologie), Réplication virale, Serine endopeptidases (déficit), Serine endopeptidases (métabolisme), Souris, Souris de lignée C57BL, Souris knockout, Sous-type H1N1 du virus de la grippe A (physiologie), Sous-type H3N2 du virus de la grippe A (physiologie), Sous-type H5N1 du virus de la grippe A (physiologie), Sous-type H7N9 du virus de la grippe A (physiologie).
- MESH :
- anatomopathologie : Infections à Orthomyxoviridae.
- déficit : Serine endopeptidases.
- métabolisme : Glycoprotéine hémagglutinine du virus influenza, Serine endopeptidases.
- physiologie : Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Sous-type H5N1 du virus de la grippe A, Sous-type H7N9 du virus de la grippe A.
- virologie : Infections à Orthomyxoviridae, Poumon.
- Analyse de survie, Animaux, Dose létale 50, Femelle, Interactions hôte-pathogène, Modèles animaux de maladie humaine, Réplication virale, Souris, Souris de lignée C57BL, Souris knockout.
English descriptors
- KwdEn :
- Animals, Disease Models, Animal, Female, Hemagglutinin Glycoproteins, Influenza Virus (metabolism), Host-Pathogen Interactions, Influenza A Virus, H1N1 Subtype (physiology), Influenza A Virus, H3N2 Subtype (physiology), Influenza A Virus, H5N1 Subtype (physiology), Influenza A Virus, H7N9 Subtype (physiology), Lethal Dose 50, Lung (virology), Mice, Mice, Inbred C57BL, Mice, Knockout, Orthomyxoviridae Infections (pathology), Orthomyxoviridae Infections (virology), Serine Endopeptidases (deficiency), Serine Endopeptidases (metabolism), Survival Analysis, Virus Replication.
- MESH :
- chemical , deficiency : Serine Endopeptidases.
- chemical , metabolism : Hemagglutinin Glycoproteins, Influenza Virus, Serine Endopeptidases.
- pathology : Orthomyxoviridae Infections.
- physiology : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza A Virus, H5N1 Subtype, Influenza A Virus, H7N9 Subtype.
- virology : Lung, Orthomyxoviridae Infections.
- Animals, Disease Models, Animal, Female, Host-Pathogen Interactions, Lethal Dose 50, Mice, Mice, Inbred C57BL, Mice, Knockout, Survival Analysis, Virus Replication.
Abstract
Proteolytic cleavage of the hemagglutinin (HA) protein is essential for influenza A virus (IAV) to acquire infectivity. This process is mediated by a host cell protease(s) in vivo. The type II transmembrane serine protease TMPRSS2 is expressed in the respiratory tract and is capable of activating a variety of respiratory viruses, including low-pathogenic (LP) IAVs possessing a single arginine residue at the cleavage site. Here we show that TMPRSS2 plays an essential role in the proteolytic activation of LP IAVs, including a recently emerged H7N9 subtype, in vivo. We generated TMPRSS2 knockout (KO) mice. The TMPRSS2 KO mice showed normal reproduction, development, and growth phenotypes. In TMPRSS2 KO mice infected with LP IAVs, cleavage of HA was severely impaired, and consequently, the majority of LP IAV progeny particles failed to gain infectivity, while the viruses were fully activated proteolytically in TMPRSS2+/+ wild-type (WT) mice. Accordingly, in contrast to WT mice, TMPRSS2 KO mice were highly tolerant of challenge infection by LP IAVs (H1N1, H3N2, and H7N9) with ≥1,000 50% lethal doses (LD50) for WT mice. On the other hand, a high-pathogenic H5N1 subtype IAV possessing a multibasic cleavage site was successfully activated in the lungs of TMPRSS2 KO mice and killed these mice, as observed for WT mice. Our results demonstrate that recently emerged H7N9 as well as seasonal IAVs mainly use the specific protease TMPRSS2 for HA cleavage in vivo and, thus, that TMPRSS2 expression is essential for IAV replication in vivo.
DOI: 10.1128/JVI.03677-13
PubMed: 24600012
Affiliations:
- Japon, États-Unis
- Région de Kantō, Wisconsin
- Madison (Wisconsin), Tokyo
- Université du Wisconsin à Madison
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Le document en format XML
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Ami</name></author><author><name sortKey="Tahara, Maino" sort="Tahara, Maino" uniqKey="Tahara M" first="Maino" last="Tahara">Maino Tahara</name></author><author><name sortKey="Kubota, Toru" sort="Kubota, Toru" uniqKey="Kubota T" first="Toru" last="Kubota">Toru Kubota</name></author><author><name sortKey="Anraku, Masaki" sort="Anraku, Masaki" uniqKey="Anraku M" first="Masaki" last="Anraku">Masaki Anraku</name></author><author><name sortKey="Abe, Masako" sort="Abe, Masako" uniqKey="Abe M" first="Masako" last="Abe">Masako Abe</name></author><author><name sortKey="Nakajima, Noriko" sort="Nakajima, Noriko" uniqKey="Nakajima N" first="Noriko" last="Nakajima">Noriko Nakajima</name></author><author><name sortKey="Sekizuka, Tsuyoshi" sort="Sekizuka, Tsuyoshi" uniqKey="Sekizuka T" first="Tsuyoshi" last="Sekizuka">Tsuyoshi Sekizuka</name></author><author><name sortKey="Shirato, Kazuya" sort="Shirato, Kazuya" uniqKey="Shirato K" first="Kazuya" last="Shirato">Kazuya Shirato</name></author><author><name sortKey="Suzaki, Yuriko" sort="Suzaki, Yuriko" uniqKey="Suzaki Y" first="Yuriko" last="Suzaki">Yuriko Suzaki</name></author><author><name sortKey="Ainai, Akira" sort="Ainai, Akira" uniqKey="Ainai A" first="Akira" last="Ainai">Akira Ainai</name></author><author><name sortKey="Nakatsu, Yuichiro" sort="Nakatsu, Yuichiro" uniqKey="Nakatsu Y" first="Yuichiro" last="Nakatsu">Yuichiro Nakatsu</name></author><author><name sortKey="Kanou, Kazuhiko" sort="Kanou, Kazuhiko" uniqKey="Kanou K" first="Kazuhiko" last="Kanou">Kazuhiko Kanou</name></author><author><name sortKey="Nakamura, Kazuya" sort="Nakamura, Kazuya" uniqKey="Nakamura K" first="Kazuya" last="Nakamura">Kazuya Nakamura</name></author><author><name sortKey="Suzuki, Tadaki" sort="Suzuki, Tadaki" uniqKey="Suzuki T" first="Tadaki" last="Suzuki">Tadaki Suzuki</name></author><author><name sortKey="Komase, Katsuhiro" sort="Komase, Katsuhiro" uniqKey="Komase K" first="Katsuhiro" last="Komase">Katsuhiro Komase</name></author><author><name sortKey="Nobusawa, Eri" sort="Nobusawa, Eri" uniqKey="Nobusawa E" first="Eri" last="Nobusawa">Eri Nobusawa</name></author><author><name sortKey="Maenaka, Katsumi" sort="Maenaka, Katsumi" uniqKey="Maenaka K" first="Katsumi" last="Maenaka">Katsumi Maenaka</name></author><author><name sortKey="Kuroda, Makoto" sort="Kuroda, Makoto" uniqKey="Kuroda M" first="Makoto" last="Kuroda">Makoto Kuroda</name></author><author><name sortKey="Hasegawa, Hideki" sort="Hasegawa, Hideki" uniqKey="Hasegawa H" first="Hideki" last="Hasegawa">Hideki Hasegawa</name></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation><country>États-Unis</country><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation></author><author><name sortKey="Tashiro, Masato" sort="Tashiro, Masato" uniqKey="Tashiro M" first="Masato" last="Tashiro">Masato Tashiro</name></author><author><name sortKey="Takeda, Makoto" sort="Takeda, Makoto" uniqKey="Takeda M" first="Makoto" last="Takeda">Makoto Takeda</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Hemagglutinin Glycoproteins, Influenza Virus (metabolism)</term><term>Host-Pathogen Interactions</term><term>Influenza A Virus, H1N1 Subtype (physiology)</term><term>Influenza A Virus, H3N2 Subtype (physiology)</term><term>Influenza A Virus, H5N1 Subtype (physiology)</term><term>Influenza A Virus, H7N9 Subtype (physiology)</term><term>Lethal Dose 50</term><term>Lung (virology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Orthomyxoviridae Infections (pathology)</term><term>Orthomyxoviridae Infections (virology)</term><term>Serine Endopeptidases (deficiency)</term><term>Serine Endopeptidases (metabolism)</term><term>Survival Analysis</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Dose létale 50</term><term>Femelle</term><term>Glycoprotéine hémagglutinine du virus influenza (métabolisme)</term><term>Infections à Orthomyxoviridae (anatomopathologie)</term><term>Infections à Orthomyxoviridae (virologie)</term><term>Interactions hôte-pathogène</term><term>Modèles animaux de maladie humaine</term><term>Poumon (virologie)</term><term>Réplication virale</term><term>Serine endopeptidases (déficit)</term><term>Serine endopeptidases (métabolisme)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Sous-type H1N1 du virus de la grippe A (physiologie)</term><term>Sous-type H3N2 du virus de la grippe A (physiologie)</term><term>Sous-type H5N1 du virus de la grippe A (physiologie)</term><term>Sous-type H7N9 du virus de la grippe A (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Hemagglutinin Glycoproteins, Influenza Virus</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à Orthomyxoviridae</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Serine endopeptidases</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéine hémagglutinine du virus influenza</term><term>Serine endopeptidases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Sous-type H5N1 du virus de la grippe A</term><term>Sous-type H7N9 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term><term>Influenza A Virus, H5N1 Subtype</term><term>Influenza A Virus, H7N9 Subtype</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à Orthomyxoviridae</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Host-Pathogen Interactions</term><term>Lethal Dose 50</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Survival Analysis</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Dose létale 50</term><term>Femelle</term><term>Interactions hôte-pathogène</term><term>Modèles animaux de maladie humaine</term><term>Réplication virale</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Proteolytic cleavage of the hemagglutinin (HA) protein is essential for influenza A virus (IAV) to acquire infectivity. This process is mediated by a host cell protease(s) in vivo. The type II transmembrane serine protease TMPRSS2 is expressed in the respiratory tract and is capable of activating a variety of respiratory viruses, including low-pathogenic (LP) IAVs possessing a single arginine residue at the cleavage site. Here we show that TMPRSS2 plays an essential role in the proteolytic activation of LP IAVs, including a recently emerged H7N9 subtype, in vivo. We generated TMPRSS2 knockout (KO) mice. The TMPRSS2 KO mice showed normal reproduction, development, and growth phenotypes. In TMPRSS2 KO mice infected with LP IAVs, cleavage of HA was severely impaired, and consequently, the majority of LP IAV progeny particles failed to gain infectivity, while the viruses were fully activated proteolytically in TMPRSS2+/+ wild-type (WT) mice. Accordingly, in contrast to WT mice, TMPRSS2 KO mice were highly tolerant of challenge infection by LP IAVs (H1N1, H3N2, and H7N9) with ≥1,000 50% lethal doses (LD50) for WT mice. On the other hand, a high-pathogenic H5N1 subtype IAV possessing a multibasic cleavage site was successfully activated in the lungs of TMPRSS2 KO mice and killed these mice, as observed for WT mice. Our results demonstrate that recently emerged H7N9 as well as seasonal IAVs mainly use the specific protease TMPRSS2 for HA cleavage in vivo and, thus, that TMPRSS2 expression is essential for IAV replication in vivo.</div></front></TEI><affiliations><list><country><li>Japon</li><li>États-Unis</li></country><region><li>Région de Kantō</li><li>Wisconsin</li></region><settlement><li>Madison (Wisconsin)</li><li>Tokyo</li></settlement><orgName><li>Université du Wisconsin à Madison</li></orgName></list><tree><noCountry><name sortKey="Abe, Masako" sort="Abe, Masako" uniqKey="Abe M" first="Masako" last="Abe">Masako Abe</name><name sortKey="Ainai, Akira" sort="Ainai, Akira" uniqKey="Ainai A" first="Akira" last="Ainai">Akira Ainai</name><name sortKey="Ami, Yasushi" sort="Ami, Yasushi" uniqKey="Ami Y" first="Yasushi" last="Ami">Yasushi Ami</name><name sortKey="Anraku, Masaki" sort="Anraku, Masaki" uniqKey="Anraku M" first="Masaki" last="Anraku">Masaki Anraku</name><name sortKey="Hasegawa, Hideki" sort="Hasegawa, Hideki" uniqKey="Hasegawa H" first="Hideki" last="Hasegawa">Hideki Hasegawa</name><name sortKey="Kanou, Kazuhiko" sort="Kanou, Kazuhiko" uniqKey="Kanou K" first="Kazuhiko" last="Kanou">Kazuhiko Kanou</name><name sortKey="Komase, Katsuhiro" sort="Komase, Katsuhiro" uniqKey="Komase K" first="Katsuhiro" last="Komase">Katsuhiro Komase</name><name sortKey="Kubota, Toru" sort="Kubota, Toru" uniqKey="Kubota T" first="Toru" last="Kubota">Toru Kubota</name><name sortKey="Kuroda, Makoto" sort="Kuroda, Makoto" uniqKey="Kuroda M" first="Makoto" last="Kuroda">Makoto Kuroda</name><name sortKey="Maenaka, Katsumi" sort="Maenaka, Katsumi" uniqKey="Maenaka K" first="Katsumi" last="Maenaka">Katsumi Maenaka</name><name sortKey="Nakajima, Noriko" sort="Nakajima, Noriko" uniqKey="Nakajima N" first="Noriko" last="Nakajima">Noriko Nakajima</name><name sortKey="Nakamura, Kazuya" sort="Nakamura, Kazuya" uniqKey="Nakamura K" first="Kazuya" last="Nakamura">Kazuya Nakamura</name><name sortKey="Nakatsu, Yuichiro" sort="Nakatsu, Yuichiro" uniqKey="Nakatsu Y" first="Yuichiro" last="Nakatsu">Yuichiro Nakatsu</name><name sortKey="Nobusawa, Eri" sort="Nobusawa, Eri" uniqKey="Nobusawa E" first="Eri" last="Nobusawa">Eri Nobusawa</name><name sortKey="Sekizuka, Tsuyoshi" sort="Sekizuka, Tsuyoshi" uniqKey="Sekizuka T" first="Tsuyoshi" last="Sekizuka">Tsuyoshi Sekizuka</name><name sortKey="Shirato, Kazuya" sort="Shirato, Kazuya" uniqKey="Shirato K" first="Kazuya" last="Shirato">Kazuya Shirato</name><name sortKey="Suzaki, Yuriko" sort="Suzaki, Yuriko" uniqKey="Suzaki Y" first="Yuriko" last="Suzaki">Yuriko Suzaki</name><name sortKey="Suzuki, Tadaki" sort="Suzuki, Tadaki" uniqKey="Suzuki T" first="Tadaki" last="Suzuki">Tadaki Suzuki</name><name sortKey="Tahara, Maino" sort="Tahara, Maino" uniqKey="Tahara M" first="Maino" last="Tahara">Maino Tahara</name><name sortKey="Takeda, Makoto" sort="Takeda, Makoto" uniqKey="Takeda M" first="Makoto" last="Takeda">Makoto Takeda</name><name sortKey="Tashiro, Masato" sort="Tashiro, Masato" uniqKey="Tashiro M" first="Masato" last="Tashiro">Masato Tashiro</name></noCountry><country name="Japon"><region name="Région de Kantō"><name sortKey="Sakai, Kouji" sort="Sakai, Kouji" uniqKey="Sakai K" first="Kouji" last="Sakai">Kouji Sakai</name></region></country><country name="États-Unis"><region name="Wisconsin"><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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