Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.

<h4>Background</h4>Cyclosporin A (CsA) is well known as an immunosuppressive drug useful for allogeneic transplantation. It has been reported that CsA inhibits hepatitis C virus (HCV) genome replication, which indicates that cellular targets of CsA regulate the viral replication. However...

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Autores principales:	Kengo Morohashi, Hiroeki Sahara, Koichi Watashi, Kazuki Iwabata, Takashi Sunoki, Kouji Kuramochi, Kaori Takakusagi, Hiroki Miyashita, Noriyuki Sato, Atsushi Tanabe, Kunitada Shimotohno, Susumu Kobayashi, Kengo Sakaguchi, Fumio Sugawara
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4678f08216734559a094713ac530e582
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spelling	oai:doaj.org-article:4678f08216734559a094713ac530e5822021-11-18T06:54:37ZCyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.1932-620310.1371/journal.pone.0018285https://doaj.org/article/4678f08216734559a094713ac530e5822011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21559518/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Cyclosporin A (CsA) is well known as an immunosuppressive drug useful for allogeneic transplantation. It has been reported that CsA inhibits hepatitis C virus (HCV) genome replication, which indicates that cellular targets of CsA regulate the viral replication. However, the regulation mechanisms of HCV replication governed by CsA target proteins have not been fully understood.<h4>Principal findings</h4>Here we show a chemical biology approach that elucidates a novel mechanism of HCV replication. We developed a phage display screening to investigate compound-peptide interaction and identified a novel cellular target molecule of CsA. This protein, named CsA associated helicase-like protein (CAHL), possessed RNA-dependent ATPase activity that was negated by treatment with CsA. The downregulation of CAHL in the cells resulted in a decrease of HCV genome replication. CAHL formed a complex with HCV-derived RNA polymerase NS5B and host-derived cyclophilin B (CyPB), known as a cellular cofactor for HCV replication, to regulate NS5B-CyPB interaction.<h4>Conclusions</h4>We found a cellular factor, CAHL, as CsA associated helicase-like protein, which would form trimer complex with CyPB and NS5B of HCV. The strategy using a chemical compound and identifying its target molecule by our phage display analysis is useful to reveal a novel mechanism underlying cellular and viral physiology.Kengo MorohashiHiroeki SaharaKoichi WatashiKazuki IwabataTakashi SunokiKouji KuramochiKaori TakakusagiHiroki MiyashitaNoriyuki SatoAtsushi TanabeKunitada ShimotohnoSusumu KobayashiKengo SakaguchiFumio SugawaraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18285 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kengo Morohashi Hiroeki Sahara Koichi Watashi Kazuki Iwabata Takashi Sunoki Kouji Kuramochi Kaori Takakusagi Hiroki Miyashita Noriyuki Sato Atsushi Tanabe Kunitada Shimotohno Susumu Kobayashi Kengo Sakaguchi Fumio Sugawara Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.
description	<h4>Background</h4>Cyclosporin A (CsA) is well known as an immunosuppressive drug useful for allogeneic transplantation. It has been reported that CsA inhibits hepatitis C virus (HCV) genome replication, which indicates that cellular targets of CsA regulate the viral replication. However, the regulation mechanisms of HCV replication governed by CsA target proteins have not been fully understood.<h4>Principal findings</h4>Here we show a chemical biology approach that elucidates a novel mechanism of HCV replication. We developed a phage display screening to investigate compound-peptide interaction and identified a novel cellular target molecule of CsA. This protein, named CsA associated helicase-like protein (CAHL), possessed RNA-dependent ATPase activity that was negated by treatment with CsA. The downregulation of CAHL in the cells resulted in a decrease of HCV genome replication. CAHL formed a complex with HCV-derived RNA polymerase NS5B and host-derived cyclophilin B (CyPB), known as a cellular cofactor for HCV replication, to regulate NS5B-CyPB interaction.<h4>Conclusions</h4>We found a cellular factor, CAHL, as CsA associated helicase-like protein, which would form trimer complex with CyPB and NS5B of HCV. The strategy using a chemical compound and identifying its target molecule by our phage display analysis is useful to reveal a novel mechanism underlying cellular and viral physiology.
format	article
author	Kengo Morohashi Hiroeki Sahara Koichi Watashi Kazuki Iwabata Takashi Sunoki Kouji Kuramochi Kaori Takakusagi Hiroki Miyashita Noriyuki Sato Atsushi Tanabe Kunitada Shimotohno Susumu Kobayashi Kengo Sakaguchi Fumio Sugawara
author_facet	Kengo Morohashi Hiroeki Sahara Koichi Watashi Kazuki Iwabata Takashi Sunoki Kouji Kuramochi Kaori Takakusagi Hiroki Miyashita Noriyuki Sato Atsushi Tanabe Kunitada Shimotohno Susumu Kobayashi Kengo Sakaguchi Fumio Sugawara
author_sort	Kengo Morohashi
title	Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.
title_short	Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.
title_full	Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.
title_fullStr	Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.
title_full_unstemmed	Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.
title_sort	cyclosporin a associated helicase-like protein facilitates the association of hepatitis c virus rna polymerase with its cellular cyclophilin b.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/4678f08216734559a094713ac530e582
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Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.

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