title: Selective recruitment of host factors by HSV-1 replication centers.
abstract: Herpes simplex virus type 1 (HSV-1) enters productive infection after infecting epithelial cells, where it controls the host nucleus to make viral proteins, starts viral DNA synthesis and assembles infectious virions. In this process, replicating viral genomes are organized into replication centers to facilitate viral growth. HSV-1 is known to use host factors, including host chromatin and host transcription regulators, to transcribe its genes; however, the invading virus also encounters host defense and stress responses to inhibit viral growth. Recently, we found that HSV-1 replication centers recruit host factor CTCF but exclude γH2A.X. Thus, HSV-1 replication centers may selectively recruit cellular factors needed for viral growth, while excluding host factors that are deleterious for viral transcription or replication. Here we report that the viral replication centers selectively excluded modified histone H3, including heterochromatin mark H3K9me3, H3S10P and active chromatin mark H3K4me3, but not unmodified H3. We found a dynamic association between the viral replication centers and host RNA polymerase II. The centers also recruited components of the DNA damage response pathway, including 53BP1, BRCA1 and host antiviral protein SP100. Importantly, we found that ATM kinase was needed for the recruitment of CTCF to the viral centers. These results suggest that the HSV-1 replication centers took advantage of host signaling pathways to actively recruit or exclude host factors to benefit viral growth.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China;University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Feng-Chao
authors.initials: FC
authors.lastname: Lang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China;University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: The Wistar Institute, Gene Expression and Regulation Program, Philadelphia PA 19104, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Vladmirova
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China;University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhuo-Ran
authors.initials: ZR
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China.
authors.forename: Gui-Jun
authors.initials: GJ
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China;University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Lu
authors.affiliation: Biology & Chemistry Engineering College, Panzhihua University, Panzhihua Sichuan 617000, China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Han
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China. zhoujm@mail.kiz.ac.cn.
authors.forename: Ju-Min
authors.initials: JM
authors.lastname: Zhou
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D004261:DNA Replication; D006561:Herpes Simplex / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D001324:Autoantigens; D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D006657:Histones; D012097:Repressor Proteins; D014764:Viral Proteins; C066642:SP100 protein, human; D012319:RNA Polymerase II
keywords: CTCF; HSV-1; RNA Pol II; Viral replication cente; γH2AX