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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Veröffentlicht in:PloS one 2019-09, Vol.14 (9), p.e0222519-e0222519
Hauptverfasser: Sugimoto, Atsuko, Yamashita, Yoriko, Kanda, Teru, Murata, Takayuki, Tsurumi, Tatsuya
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Yamashita, Yoriko
Kanda, Teru
Murata, Takayuki
Tsurumi, Tatsuya
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.</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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