TMPRSS2 Isoform 1 Activates Respiratory Viruses and Is Expressed in Viral Target Cells
Identifieur interne : 001229 ( Main/Exploration ); précédent : 001228; suivant : 001230TMPRSS2 Isoform 1 Activates Respiratory Viruses and Is Expressed in Viral Target Cells
Auteurs : Pawel Zmora ; Anna-Sophie Moldenhauer ; Heike Hofmann-Winkler ; Stefan PöhlmannSource :
- PLoS ONE [ 1932-6203 ] ; 2015.
Descripteurs français
- KwdFr :
- ARN messager (métabolisme), Animaux, Cathepsines (métabolisme), Cellules COS, Cellules Caco-2, Cellules HEK293, Glycoprotéine de spicule des coronavirus (métabolisme), Humains, Hémagglutinines (métabolisme), Interactions hôte-pathogène (physiologie), Isoformes de protéines (métabolisme), Lignée cellulaire, Orthomyxoviridae (métabolisme), Poumon (métabolisme), Poumon (virologie), Pénétration virale, Serine endopeptidases (métabolisme), Virus du SRAS (métabolisme).
- MESH :
- métabolisme : ARN messager, Cathepsines, Glycoprotéine de spicule des coronavirus, Hémagglutinines, Isoformes de protéines, Orthomyxoviridae, Poumon, Serine endopeptidases, Virus du SRAS.
- physiologie : Interactions hôte-pathogène.
- virologie : Poumon.
- Animaux, Cellules COS, Cellules Caco-2, Cellules HEK293, Humains, Lignée cellulaire, Pénétration virale.
English descriptors
- KwdEn :
- Animals, COS Cells, Caco-2 Cells, Cathepsins (metabolism), Cell Line, Chlorocebus aethiops, HEK293 Cells, Hemagglutinins (metabolism), Host-Pathogen Interactions (physiology), Humans, Lung (metabolism), Lung (virology), Orthomyxoviridae (metabolism), Protein Isoforms (metabolism), RNA, Messenger (metabolism), SARS Virus (metabolism), Serine Endopeptidases (metabolism), Spike Glycoprotein, Coronavirus (metabolism), Virus Internalization.
- MESH :
- chemical , metabolism : Cathepsins, Hemagglutinins, Protein Isoforms, RNA, Messenger, Serine Endopeptidases, Spike Glycoprotein, Coronavirus.
- metabolism : Lung, Orthomyxoviridae, SARS Virus.
- physiology : Host-Pathogen Interactions.
- virology : Lung.
- Animals, COS Cells, Caco-2 Cells, Cell Line, Chlorocebus aethiops, HEK293 Cells, Humans, Virus Internalization.
Abstract
The cellular protease TMPRSS2 cleaves and activates the influenza virus hemagglutinin (HA) and TMPRSS2 expression is essential for viral spread and pathogenesis in mice. Moreover, severe acute respiratory syndrome coronavirus (SARS-CoV) and other respiratory viruses are activated by TMPRSS2. However, previous studies on viral activation by TMPRSS2 focused on a 492 amino acids comprising form of the protein (isoform 2) while other TMPRSS2 isoforms, generated upon alternative splicing of the tmprss2 mRNA, have not been characterized. Here, we show that the mRNA encoding a TMPRSS2 isoform with an extended N-terminal cytoplasmic domain (isoform 1) is expressed in lung-derived cell lines and tissues. Moreover, we demonstrate that TMPRSS2 isoform 1 colocalizes with HA and cleaves and activates HA. Finally, we show that isoform 1 activates the SARS-CoV spike protein for cathepsin L-independent entry into target cells. Our results indicate that TMPRSS2 isoform 1 is expressed in viral target cells and might contribute to viral activation in the host.
Url:
DOI: 10.1371/journal.pone.0138380
PubMed: 26379044
PubMed Central: 4574978
Affiliations:
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(métabolisme)</term><term>Interactions hôte-pathogène (physiologie)</term><term>Isoformes de protéines (métabolisme)</term><term>Lignée cellulaire</term><term>Orthomyxoviridae (métabolisme)</term><term>Poumon (métabolisme)</term><term>Poumon (virologie)</term><term>Pénétration virale</term><term>Serine endopeptidases (métabolisme)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cathepsins</term><term>Hemagglutinins</term><term>Protein Isoforms</term><term>RNA, Messenger</term><term>Serine Endopeptidases</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term><term>Orthomyxoviridae</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN messager</term><term>Cathepsines</term><term>Glycoprotéine de spicule des 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HEK293</term><term>Humains</term><term>Lignée cellulaire</term><term>Pénétration virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The cellular protease TMPRSS2 cleaves and activates the influenza virus hemagglutinin (HA) and TMPRSS2 expression is essential for viral spread and pathogenesis in mice. Moreover, severe acute respiratory syndrome coronavirus (SARS-CoV) and other respiratory viruses are activated by TMPRSS2. However, previous studies on viral activation by TMPRSS2 focused on a 492 amino acids comprising form of the protein (isoform 2) while other TMPRSS2 isoforms, generated upon alternative splicing of the tmprss2 mRNA, have not been characterized. Here, we show that the mRNA encoding a TMPRSS2 isoform with an extended N-terminal cytoplasmic domain (isoform 1) is expressed in lung-derived cell lines and tissues. Moreover, we demonstrate that TMPRSS2 isoform 1 colocalizes with HA and cleaves and activates HA. Finally, we show that isoform 1 activates the SARS-CoV spike protein for cathepsin L-independent entry into target cells. Our results indicate that TMPRSS2 isoform 1 is expressed in viral target cells and might contribute to viral activation in the host.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Kash, Jc" uniqKey="Kash J">JC Kash</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morens, Dm" uniqKey="Morens D">DM Morens</name></author><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Harvey, Ha" uniqKey="Harvey H">HA Harvey</name></author><author><name sortKey="Memoli, Mj" uniqKey="Memoli M">MJ Memoli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Edinger, To" uniqKey="Edinger T">TO Edinger</name></author><author><name sortKey="Pohl, Mo" uniqKey="Pohl M">MO Pohl</name></author><author><name sortKey="Stertz, S" 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Nehlmeier</name></author><author><name sortKey="Wu, Q" uniqKey="Wu Q">Q Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matthaei, M" uniqKey="Matthaei M">M Matthaei</name></author><author><name sortKey="Budt, M" uniqKey="Budt M">M Budt</name></author><author><name sortKey="Wolff, T" uniqKey="Wolff T">T Wolff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wrensch, F" uniqKey="Wrensch F">F Wrensch</name></author><author><name sortKey="Winkler, M" uniqKey="Winkler M">M Winkler</name></author><author><name sortKey="Pohlmann, S" uniqKey="Pohlmann S">S Pöhlmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vaarala, Mh" uniqKey="Vaarala M">MH Vaarala</name></author><author><name sortKey="Porvari, Ks" uniqKey="Porvari K">KS Porvari</name></author><author><name sortKey="Kellokumpu, S" uniqKey="Kellokumpu S">S Kellokumpu</name></author><author><name sortKey="Kyllonen, Ap" uniqKey="Kyllonen A">AP Kyllonen</name></author><author><name sortKey="Vihko, Pt" uniqKey="Vihko P">PT Vihko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gierer, S" uniqKey="Gierer S">S Gierer</name></author><author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name></author><author><name sortKey="Kaup, F" uniqKey="Kaup F">F Kaup</name></author><author><name sortKey="Wrensch, F" uniqKey="Wrensch F">F Wrensch</name></author><author><name sortKey="Heurich, A" uniqKey="Heurich A">A Heurich</name></author><author><name sortKey="Kramer Kuhl, A" uniqKey="Kramer Kuhl A">A Kramer-Kühl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K Shirato</name></author><author><name sortKey="Kawase, M" uniqKey="Kawase M">M Kawase</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simmons, G" uniqKey="Simmons G">G Simmons</name></author><author><name sortKey="Gosalia, Dn" uniqKey="Gosalia D">DN Gosalia</name></author><author><name sortKey="Rennekamp, Aj" uniqKey="Rennekamp A">AJ Rennekamp</name></author><author><name sortKey="Reeves, Jd" uniqKey="Reeves J">JD Reeves</name></author><author><name sortKey="Diamond, Sl" uniqKey="Diamond S">SL Diamond</name></author><author><name sortKey="Bates, P" uniqKey="Bates P">P Bates</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name></author><author><name sortKey="Heurich, A" uniqKey="Heurich A">A Heurich</name></author><author><name sortKey="Lavender, H" uniqKey="Lavender H">H Lavender</name></author><author><name sortKey="Gierer, S" uniqKey="Gierer S">S Gierer</name></author><author><name sortKey="Danisch, S" uniqKey="Danisch S">S Danisch</name></author><author><name sortKey="Perin, P" uniqKey="Perin P">P Perin</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Hofmann Winkler, Heike" sort="Hofmann Winkler, Heike" uniqKey="Hofmann Winkler H" first="Heike" last="Hofmann-Winkler">Heike Hofmann-Winkler</name><name sortKey="Moldenhauer, Anna Sophie" sort="Moldenhauer, Anna Sophie" uniqKey="Moldenhauer A" first="Anna-Sophie" last="Moldenhauer">Anna-Sophie Moldenhauer</name><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name><name sortKey="Zmora, Pawel" sort="Zmora, Pawel" uniqKey="Zmora P" first="Pawel" last="Zmora">Pawel Zmora</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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