An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.

Glutathione (GSH) is the most abundant cellular thiol playing an essential role in preserving a reduced cellular environment. Cellular GSH levels can be efficiently reduced by the GSH biosynthesis inhibitor, L-buthionine sulfoximine (BSO). The aim of our study was to determine the role of GSH in the...

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Autores principales:	Hsin-Chieh Ma, Ying Liu, Chunling Wang, Michael Strauss, Nina Rehage, Ying-Han Chen, Nihal Altan-Bonnet, James Hogle, Eckard Wimmer, Steffen Mueller, Aniko V Paul, Ping Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a6d83bff16384729b183bf81004b6578
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spelling	oai:doaj.org-article:a6d83bff16384729b183bf81004b65782021-11-18T06:06:44ZAn interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.1553-73661553-737410.1371/journal.ppat.1004052https://doaj.org/article/a6d83bff16384729b183bf81004b65782014-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24722315/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Glutathione (GSH) is the most abundant cellular thiol playing an essential role in preserving a reduced cellular environment. Cellular GSH levels can be efficiently reduced by the GSH biosynthesis inhibitor, L-buthionine sulfoximine (BSO). The aim of our study was to determine the role of GSH in the growth of two C-cluster enteroviruses, poliovirus type 1 (PV1) and coxsackievirus A20 (CAV20). Our results show that the growth of both PV1 and CAV20 is strongly inhibited by BSO and can be partially reversed by the addition of GSH. BSO has no effect on viral protein synthesis or RNA replication but it strikingly reduces the accumulation of 14S pentamers in infected cells. GSH-pull down assays show that GSH directly interacts with capsid precursors and mature virus made in the absence of BSO whereas capsid precursors produced under GSH-depletion do not bind to GSH. In particular, the loss of binding of GSH may debilitate the stability of 14S pentamers, resulting in their failure to assemble into mature virus. Immunofluorescence cell imaging demonstrated that GSH-depletion did not affect the localization of viral capsid proteins to the replication complex. PV1 BSO resistant (BSOr) mutants evolved readily during passaging of the virus in the presence of BSO. Structural analyses revealed that the BSOr mutations, mapping to VP1 and VP3 capsid proteins, are primarily located at protomer/protomer interfaces. BSOr mutations might, in place of GSH, aid the stability of 14S particles that is required for virion maturation. Our observation that BSOr mutants are more heat resistant and need less GSH than wt virus to be protected from heat inactivation suggests that they possess a more stable capsid. We propose that the role of GSH during enterovirus morphogenesis is to stabilize capsid structures by direct interaction with capsid proteins both during and after the formation of mature virus particles.Hsin-Chieh MaYing LiuChunling WangMichael StraussNina RehageYing-Han ChenNihal Altan-BonnetJames HogleEckard WimmerSteffen MuellerAniko V PaulPing JiangPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 4, p e1004052 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Hsin-Chieh Ma Ying Liu Chunling Wang Michael Strauss Nina Rehage Ying-Han Chen Nihal Altan-Bonnet James Hogle Eckard Wimmer Steffen Mueller Aniko V Paul Ping Jiang An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.
description	Glutathione (GSH) is the most abundant cellular thiol playing an essential role in preserving a reduced cellular environment. Cellular GSH levels can be efficiently reduced by the GSH biosynthesis inhibitor, L-buthionine sulfoximine (BSO). The aim of our study was to determine the role of GSH in the growth of two C-cluster enteroviruses, poliovirus type 1 (PV1) and coxsackievirus A20 (CAV20). Our results show that the growth of both PV1 and CAV20 is strongly inhibited by BSO and can be partially reversed by the addition of GSH. BSO has no effect on viral protein synthesis or RNA replication but it strikingly reduces the accumulation of 14S pentamers in infected cells. GSH-pull down assays show that GSH directly interacts with capsid precursors and mature virus made in the absence of BSO whereas capsid precursors produced under GSH-depletion do not bind to GSH. In particular, the loss of binding of GSH may debilitate the stability of 14S pentamers, resulting in their failure to assemble into mature virus. Immunofluorescence cell imaging demonstrated that GSH-depletion did not affect the localization of viral capsid proteins to the replication complex. PV1 BSO resistant (BSOr) mutants evolved readily during passaging of the virus in the presence of BSO. Structural analyses revealed that the BSOr mutations, mapping to VP1 and VP3 capsid proteins, are primarily located at protomer/protomer interfaces. BSOr mutations might, in place of GSH, aid the stability of 14S particles that is required for virion maturation. Our observation that BSOr mutants are more heat resistant and need less GSH than wt virus to be protected from heat inactivation suggests that they possess a more stable capsid. We propose that the role of GSH during enterovirus morphogenesis is to stabilize capsid structures by direct interaction with capsid proteins both during and after the formation of mature virus particles.
format	article
author	Hsin-Chieh Ma Ying Liu Chunling Wang Michael Strauss Nina Rehage Ying-Han Chen Nihal Altan-Bonnet James Hogle Eckard Wimmer Steffen Mueller Aniko V Paul Ping Jiang
author_facet	Hsin-Chieh Ma Ying Liu Chunling Wang Michael Strauss Nina Rehage Ying-Han Chen Nihal Altan-Bonnet James Hogle Eckard Wimmer Steffen Mueller Aniko V Paul Ping Jiang
author_sort	Hsin-Chieh Ma
title	An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.
title_short	An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.
title_full	An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.
title_fullStr	An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.
title_full_unstemmed	An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.
title_sort	interaction between glutathione and the capsid is required for the morphogenesis of c-cluster enteroviruses.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a6d83bff16384729b183bf81004b6578
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An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses.

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