Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain

ABSTRACT The genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis through the action of a viral protein with a chromatin-tethering domain (CTD). Here, we report that the human cytomegalovirus (HCMV) genome is maintained during mitosis by the CTD of...

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Autores principales:	Shelby M. Lyon, Kristen D. Yetming, Christina Paulus, Michael Nevels, Robert F. Kalejta
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	cancer chromatin herpes latency mitosis transcription Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0a07340b1ba840cd8eb8f8c1d7c83cff
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spelling	oai:doaj.org-article:0a07340b1ba840cd8eb8f8c1d7c83cff2021-11-15T16:19:07ZHuman Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain10.1128/mBio.02410-202150-7511https://doaj.org/article/0a07340b1ba840cd8eb8f8c1d7c83cff2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02410-20https://doaj.org/toc/2150-7511ABSTRACT The genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis through the action of a viral protein with a chromatin-tethering domain (CTD). Here, we report that the human cytomegalovirus (HCMV) genome is maintained during mitosis by the CTD of the viral IE19 protein. Deletion of the IE19 CTD or disruption of the IE19 splice acceptor site reduced viral genome maintenance and progeny virion formation during infection of dividing fibroblasts, both of which were rescued by IE19 ectopic expression. The discovery of a viral genome maintenance factor during productive infection provides new insight into the mode of HCMV infection implicated in birth defects, organ transplant failure, and cancer. IMPORTANCE Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects, represents a serious complication for immunocompromised HIV/AIDS and organ transplant patients, and contributes to both immunosenescence and cardiovascular diseases. HCMV is also implicated in cancers such as glioblastoma multiforme (GBM) and infects ex vivo-cultured GBM tumor cells. In dividing tumor cells, the genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis. This mitotic survival is mediated by a viral protein with a chromatin-tethering domain (CTD). Here, we report that the HCMV genome is maintained in dividing fibroblasts by the CTD of the viral IE19 protein. The discovery of a viral genome maintenance factor during productive infection could help explain viral genome dynamics within HCMV-positive tumors as well as during latency.Shelby M. LyonKristen D. YetmingChristina PaulusMichael NevelsRobert F. KalejtaAmerican Society for MicrobiologyarticlecancerchromatinherpeslatencymitosistranscriptionMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer chromatin herpes latency mitosis transcription Microbiology QR1-502
spellingShingle	cancer chromatin herpes latency mitosis transcription Microbiology QR1-502 Shelby M. Lyon Kristen D. Yetming Christina Paulus Michael Nevels Robert F. Kalejta Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain
description	ABSTRACT The genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis through the action of a viral protein with a chromatin-tethering domain (CTD). Here, we report that the human cytomegalovirus (HCMV) genome is maintained during mitosis by the CTD of the viral IE19 protein. Deletion of the IE19 CTD or disruption of the IE19 splice acceptor site reduced viral genome maintenance and progeny virion formation during infection of dividing fibroblasts, both of which were rescued by IE19 ectopic expression. The discovery of a viral genome maintenance factor during productive infection provides new insight into the mode of HCMV infection implicated in birth defects, organ transplant failure, and cancer. IMPORTANCE Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects, represents a serious complication for immunocompromised HIV/AIDS and organ transplant patients, and contributes to both immunosenescence and cardiovascular diseases. HCMV is also implicated in cancers such as glioblastoma multiforme (GBM) and infects ex vivo-cultured GBM tumor cells. In dividing tumor cells, the genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis. This mitotic survival is mediated by a viral protein with a chromatin-tethering domain (CTD). Here, we report that the HCMV genome is maintained in dividing fibroblasts by the CTD of the viral IE19 protein. The discovery of a viral genome maintenance factor during productive infection could help explain viral genome dynamics within HCMV-positive tumors as well as during latency.
format	article
author	Shelby M. Lyon Kristen D. Yetming Christina Paulus Michael Nevels Robert F. Kalejta
author_facet	Shelby M. Lyon Kristen D. Yetming Christina Paulus Michael Nevels Robert F. Kalejta
author_sort	Shelby M. Lyon
title	Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain
title_short	Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain
title_full	Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain
title_fullStr	Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain
title_full_unstemmed	Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain
title_sort	human cytomegalovirus genomes survive mitosis via the ie19 chromatin-tethering domain
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/0a07340b1ba840cd8eb8f8c1d7c83cff
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Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain

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