BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection

ABSTRACT Simian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required f...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Edward C. Goodwin, Alex Lipovsky, Takamasa Inoue, Thomas G. Magaldi, Anne P. B. Edwards, Kristin E. Y. Van Goor, Adrienne W. Paton, James C. Paton, Walter J. Atwood, Billy Tsai, Daniel DiMaio
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7d5ff50acbcd43f9ac63ba8b338523b9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7d5ff50acbcd43f9ac63ba8b338523b9
record_format	dspace
spelling	oai:doaj.org-article:7d5ff50acbcd43f9ac63ba8b338523b92021-11-15T15:38:49ZBiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection10.1128/mBio.00101-112150-7511https://doaj.org/article/7d5ff50acbcd43f9ac63ba8b338523b92011-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00101-11https://doaj.org/toc/2150-7511ABSTRACT Simian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required for SV40 infection. SV40 infection was specifically inhibited by up to 50-fold by knockdown of four different DNAJ molecular cochaperones or by inhibition of BiP, the Hsp70 partner of DNAJB11. These proteins were not required for the initiation of capsid disassembly, but knockdown markedly inhibited SV40 exit from the ER. In addition, BiP formed a complex with SV40 capsids in the ER in a DNAJB11-dependent fashion. These experiments identify five new cellular proteins required for SV40 infection and suggest that the binding of BiP to the capsid is required for ER exit. Further studies of these proteins will provide insight into the molecular mechanisms of polyomavirus infection and ER function. IMPORTANCE The polyomaviruses, including simian virus 40 (SV40), are important human pathogens and model systems for exploring the general features of virus replication and cell biology. We used a genetic system to interrogate the role of cellular genes in SV40 infection. Based on the results of this unbiased genetic screen and analysis of proteins related to the strongest hit from the screen, we identified five new cellular proteins required for the entry of SV40 into cells. These proteins physically associate with SV40 in the endoplasmic reticulum (ER) during virus entry and are required for exit of the partially disassembled virus from this organelle. These results demonstrate that the polyomaviruses have coopted an ER-localized protein quality control process to initiate disassembly and transit through the cell on their way to the nuclear site of virus replication.Edward C. GoodwinAlex LipovskyTakamasa InoueThomas G. MagaldiAnne P. B. EdwardsKristin E. Y. Van GoorAdrienne W. PatonJames C. PatonWalter J. AtwoodBilly TsaiDaniel DiMaioAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 3 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Edward C. Goodwin Alex Lipovsky Takamasa Inoue Thomas G. Magaldi Anne P. B. Edwards Kristin E. Y. Van Goor Adrienne W. Paton James C. Paton Walter J. Atwood Billy Tsai Daniel DiMaio BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection
description	ABSTRACT Simian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required for SV40 infection. SV40 infection was specifically inhibited by up to 50-fold by knockdown of four different DNAJ molecular cochaperones or by inhibition of BiP, the Hsp70 partner of DNAJB11. These proteins were not required for the initiation of capsid disassembly, but knockdown markedly inhibited SV40 exit from the ER. In addition, BiP formed a complex with SV40 capsids in the ER in a DNAJB11-dependent fashion. These experiments identify five new cellular proteins required for SV40 infection and suggest that the binding of BiP to the capsid is required for ER exit. Further studies of these proteins will provide insight into the molecular mechanisms of polyomavirus infection and ER function. IMPORTANCE The polyomaviruses, including simian virus 40 (SV40), are important human pathogens and model systems for exploring the general features of virus replication and cell biology. We used a genetic system to interrogate the role of cellular genes in SV40 infection. Based on the results of this unbiased genetic screen and analysis of proteins related to the strongest hit from the screen, we identified five new cellular proteins required for the entry of SV40 into cells. These proteins physically associate with SV40 in the endoplasmic reticulum (ER) during virus entry and are required for exit of the partially disassembled virus from this organelle. These results demonstrate that the polyomaviruses have coopted an ER-localized protein quality control process to initiate disassembly and transit through the cell on their way to the nuclear site of virus replication.
format	article
author	Edward C. Goodwin Alex Lipovsky Takamasa Inoue Thomas G. Magaldi Anne P. B. Edwards Kristin E. Y. Van Goor Adrienne W. Paton James C. Paton Walter J. Atwood Billy Tsai Daniel DiMaio
author_facet	Edward C. Goodwin Alex Lipovsky Takamasa Inoue Thomas G. Magaldi Anne P. B. Edwards Kristin E. Y. Van Goor Adrienne W. Paton James C. Paton Walter J. Atwood Billy Tsai Daniel DiMaio
author_sort	Edward C. Goodwin
title	BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection
title_short	BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection
title_full	BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection
title_fullStr	BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection
title_full_unstemmed	BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection
title_sort	bip and multiple dnaj molecular chaperones in the endoplasmic reticulum are required for efficient simian virus 40 infection
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/7d5ff50acbcd43f9ac63ba8b338523b9
work_keys_str_mv	AT edwardcgoodwin bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT alexlipovsky bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT takamasainoue bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT thomasgmagaldi bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT annepbedwards bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT kristineyvangoor bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT adriennewpaton bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT jamescpaton bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT walterjatwood bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT billytsai bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection AT danieldimaio bipandmultiplednajmolecularchaperonesintheendoplasmicreticulumarerequiredforefficientsimianvirus40infection
_version_	1718427833626263552

BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection

Ejemplares similares