Epstein-Barr virus genome packaging factors accumulate in BMRF1-cores within viral replication compartments
Productive replication of Epstein-Barr virus (EBV) during the lytic cycle occurs in discrete sites within nuclei, termed replication compartments. We previously proposed that replication compartments consist of two subnuclear domains: "ongoing replication foci" and "BMRF1-cores"....
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description | Productive replication of Epstein-Barr virus (EBV) during the lytic cycle occurs in discrete sites within nuclei, termed replication compartments. We previously proposed that replication compartments consist of two subnuclear domains: "ongoing replication foci" and "BMRF1-cores". Viral genome replication takes place in ongoing replication foci, which are enriched with viral replication proteins, such as BALF5 and BALF2. Amplified DNA and BMRF1 protein accumulate in BMRF1-cores, which are surrounded by ongoing replication foci. We here determined the locations of procapsid and genome-packaging proteins of EBV via three-dimensional (3D) surface reconstruction and correlative fluorescence microscopy-electron microscopy (FM-EM). The results revealed that viral factors required for DNA packaging, such as BGLF1, BVRF1, and BFLF1 proteins, are located in the innermost subdomains of the BMRF1-cores. In contrast, capsid structural proteins, such as BBRF1, BORF1, BDLF1, and BVRF2, were found both outside and inside the BMRF1-cores. Based on these observations, we propose a model in which viral procapsids are assembled outside the BMRF1-cores and subsequently migrate therein, where viral DNA encapsidation occurs. To our knowledge, this is the first report describing capsid assembly sites in relation to EBV replication compartments. |
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We previously proposed that replication compartments consist of two subnuclear domains: "ongoing replication foci" and "BMRF1-cores". Viral genome replication takes place in ongoing replication foci, which are enriched with viral replication proteins, such as BALF5 and BALF2. Amplified DNA and BMRF1 protein accumulate in BMRF1-cores, which are surrounded by ongoing replication foci. We here determined the locations of procapsid and genome-packaging proteins of EBV via three-dimensional (3D) surface reconstruction and correlative fluorescence microscopy-electron microscopy (FM-EM). The results revealed that viral factors required for DNA packaging, such as BGLF1, BVRF1, and BFLF1 proteins, are located in the innermost subdomains of the BMRF1-cores. In contrast, capsid structural proteins, such as BBRF1, BORF1, BDLF1, and BVRF2, were found both outside and inside the BMRF1-cores. Based on these observations, we propose a model in which viral procapsids are assembled outside the BMRF1-cores and subsequently migrate therein, where viral DNA encapsidation occurs. To our knowledge, this is the first report describing capsid assembly sites in relation to EBV replication compartments.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0222519</identifier><identifier>PMID: 31518362</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antigens, Viral - genetics ; BMRF1 protein ; Cancer ; Cell Line ; Cell Nucleus - genetics ; Chemical bonds ; Compartments ; Cores ; Cyclin-dependent kinases ; Deoxyribonucleic acid ; DNA ; DNA polymerase ; DNA Replication - genetics ; DNA, Viral - genetics ; DNA-Binding Proteins - genetics ; Domains ; Electron microscopy ; Encapsidation ; Epstein-Barr virus ; Fluorescence ; Fluorescence microscopy ; Genes ; Genetic aspects ; Genome, Viral - genetics ; Genomes ; Genomics ; Herpes viruses ; Herpesvirus 4, Human - genetics ; Humans ; Infections ; Kinases ; Medicine ; Microscopy ; Packaging ; Parasitology ; Procapsids ; Proteins ; Replication ; Structural proteins ; Tetracyclines ; University graduates ; Viral genetics ; Viral Proteins - genetics ; Virology ; Virus replication ; Virus Replication - genetics ; Viruses</subject><ispartof>PloS one, 2019-09, Vol.14 (9), p.e0222519-e0222519</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Sugimoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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We previously proposed that replication compartments consist of two subnuclear domains: "ongoing replication foci" and "BMRF1-cores". Viral genome replication takes place in ongoing replication foci, which are enriched with viral replication proteins, such as BALF5 and BALF2. Amplified DNA and BMRF1 protein accumulate in BMRF1-cores, which are surrounded by ongoing replication foci. We here determined the locations of procapsid and genome-packaging proteins of EBV via three-dimensional (3D) surface reconstruction and correlative fluorescence microscopy-electron microscopy (FM-EM). The results revealed that viral factors required for DNA packaging, such as BGLF1, BVRF1, and BFLF1 proteins, are located in the innermost subdomains of the BMRF1-cores. In contrast, capsid structural proteins, such as BBRF1, BORF1, BDLF1, and BVRF2, were found both outside and inside the BMRF1-cores. Based on these observations, we propose a model in which viral procapsids are assembled outside the BMRF1-cores and subsequently migrate therein, where viral DNA encapsidation occurs. To our knowledge, this is the first report describing capsid assembly sites in relation to EBV replication compartments.</description><subject>Analysis</subject><subject>Antigens, Viral - genetics</subject><subject>BMRF1 protein</subject><subject>Cancer</subject><subject>Cell Line</subject><subject>Cell Nucleus - genetics</subject><subject>Chemical bonds</subject><subject>Compartments</subject><subject>Cores</subject><subject>Cyclin-dependent kinases</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA polymerase</subject><subject>DNA Replication - genetics</subject><subject>DNA, Viral - genetics</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Domains</subject><subject>Electron microscopy</subject><subject>Encapsidation</subject><subject>Epstein-Barr virus</subject><subject>Fluorescence</subject><subject>Fluorescence microscopy</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genome, Viral - genetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Herpes viruses</subject><subject>Herpesvirus 4, Human - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sugimoto, Atsuko</au><au>Yamashita, Yoriko</au><au>Kanda, Teru</au><au>Murata, Takayuki</au><au>Tsurumi, Tatsuya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epstein-Barr virus genome packaging factors accumulate in BMRF1-cores within viral replication compartments</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-09-13</date><risdate>2019</risdate><volume>14</volume><issue>9</issue><spage>e0222519</spage><epage>e0222519</epage><pages>e0222519-e0222519</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Productive replication of Epstein-Barr virus (EBV) during the lytic cycle occurs in discrete sites within nuclei, termed replication compartments. We previously proposed that replication compartments consist of two subnuclear domains: "ongoing replication foci" and "BMRF1-cores". Viral genome replication takes place in ongoing replication foci, which are enriched with viral replication proteins, such as BALF5 and BALF2. Amplified DNA and BMRF1 protein accumulate in BMRF1-cores, which are surrounded by ongoing replication foci. We here determined the locations of procapsid and genome-packaging proteins of EBV via three-dimensional (3D) surface reconstruction and correlative fluorescence microscopy-electron microscopy (FM-EM). The results revealed that viral factors required for DNA packaging, such as BGLF1, BVRF1, and BFLF1 proteins, are located in the innermost subdomains of the BMRF1-cores. In contrast, capsid structural proteins, such as BBRF1, BORF1, BDLF1, and BVRF2, were found both outside and inside the BMRF1-cores. Based on these observations, we propose a model in which viral procapsids are assembled outside the BMRF1-cores and subsequently migrate therein, where viral DNA encapsidation occurs. To our knowledge, this is the first report describing capsid assembly sites in relation to EBV replication compartments.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31518362</pmid><doi>10.1371/journal.pone.0222519</doi><tpages>e0222519</tpages><orcidid>https://orcid.org/0000-0001-7228-0839</orcidid><orcidid>https://orcid.org/0000-0002-1468-8817</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Analysis Antigens, Viral - genetics BMRF1 protein Cancer Cell Line Cell Nucleus - genetics Chemical bonds Compartments Cores Cyclin-dependent kinases Deoxyribonucleic acid DNA DNA polymerase DNA Replication - genetics DNA, Viral - genetics DNA-Binding Proteins - genetics Domains Electron microscopy Encapsidation Epstein-Barr virus Fluorescence Fluorescence microscopy Genes Genetic aspects Genome, Viral - genetics Genomes Genomics Herpes viruses Herpesvirus 4, Human - genetics Humans Infections Kinases Medicine Microscopy Packaging Parasitology Procapsids Proteins Replication Structural proteins Tetracyclines University graduates Viral genetics Viral Proteins - genetics Virology Virus replication Virus Replication - genetics Viruses |
title | Epstein-Barr virus genome packaging factors accumulate in BMRF1-cores within viral replication compartments |
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