Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA

Detalhes bibliográficos
Autor(a) principal: Habison, Aline C.
Data de Publicação: 2017
Outros Autores: Pires de Miranda, Marta, Beauchemin, Chantal, Tan, Min, A. Cerqueira, Sofia, Correia, Bruno, Ponnusamy, Rajesh, Usherwood, Edward J., McVey, Colin E., Simas, J Pedro, Kaye, Kenneth M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/54372
Resumo: Copyright: © 2017 Habison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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spelling Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANACopyright: © 2017 Habison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Many pathogens, including Kaposi's sarcoma herpesvirus (KSHV), lack tractable small animal models. KSHV persists as a multi-copy, nuclear episome in latently infected cells. KSHV latency-associated nuclear antigen (kLANA) binds viral terminal repeat (kTR) DNA to mediate episome persistence. Model pathogen murine gammaherpesvirus 68 (MHV68) mLANA acts analogously on mTR DNA. kLANA and mLANA differ substantially in size and kTR and mTR show little sequence conservation. Here, we find kLANA and mLANA act reciprocally to mediate episome persistence of TR DNA. Further, kLANA rescued mLANA deficient MHV68, enabling a chimeric virus to establish latent infection in vivo in germinal center B cells. The level of chimeric virus in vivo latency was moderately reduced compared to WT infection, but WT or chimeric MHV68 infected cells had similar viral genome copy numbers as assessed by immunofluorescence of LANA intranuclear dots or qPCR. Thus, despite more than 60 Ma of evolutionary divergence, mLANA and kLANA act reciprocally on TR DNA, and kLANA functionally substitutes for mLANA, allowing kLANA investigation in vivo. Analogous chimeras may allow in vivo investigation of genes of other human pathogens.This work was supported in part by National Institutes of Health grants CA082036 (NCI), DE025208, and DE024971 (both NIDCR), to KMK, FCT PTDC/IMI-MIC/0980/2014 to JPS, FCT Harvard Medical School Portugal Program in Translational Research (HMSP-ICT/0021/2010) to JPS, KMK, CEM, Instituto de Medicina Molecular Directors Fund to JPS, and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344) FCT/FEDER (PT2020 Partnership Agreement) to CEM. M.P.M is supported by a fellowship from Fundação para a Ciência e Tecnologia (FCT), Portugal.PLOSRepositório da Universidade de LisboaHabison, Aline C.Pires de Miranda, MartaBeauchemin, ChantalTan, MinA. Cerqueira, SofiaCorreia, BrunoPonnusamy, RajeshUsherwood, Edward J.McVey, Colin E.Simas, J PedroKaye, Kenneth M.2022-09-08T11:26:24Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54372engPLoS Pathog. 2017 Sep 14;13(9):e10065551553-736610.1371/journal.ppat.10065551553-7374info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:00:11Zoai:repositorio.ul.pt:10451/54372Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:54.427408Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA
title Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA
spellingShingle Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA
Habison, Aline C.
title_short Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA
title_full Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA
title_fullStr Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA
title_full_unstemmed Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA
title_sort Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA
author Habison, Aline C.
author_facet Habison, Aline C.
Pires de Miranda, Marta
Beauchemin, Chantal
Tan, Min
A. Cerqueira, Sofia
Correia, Bruno
Ponnusamy, Rajesh
Usherwood, Edward J.
McVey, Colin E.
Simas, J Pedro
Kaye, Kenneth M.
author_role author
author2 Pires de Miranda, Marta
Beauchemin, Chantal
Tan, Min
A. Cerqueira, Sofia
Correia, Bruno
Ponnusamy, Rajesh
Usherwood, Edward J.
McVey, Colin E.
Simas, J Pedro
Kaye, Kenneth M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Habison, Aline C.
Pires de Miranda, Marta
Beauchemin, Chantal
Tan, Min
A. Cerqueira, Sofia
Correia, Bruno
Ponnusamy, Rajesh
Usherwood, Edward J.
McVey, Colin E.
Simas, J Pedro
Kaye, Kenneth M.
description Copyright: © 2017 Habison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01T00:00:00Z
2022-09-08T11:26:24Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/54372
url http://hdl.handle.net/10451/54372
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS Pathog. 2017 Sep 14;13(9):e1006555
1553-7366
10.1371/journal.ppat.1006555
1553-7374
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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