title: Stimulation of the Replication of ICP0-Null Mutant Herpes Simplex Virus 1 and pp71-Deficient Human Cytomegalovirus by Epstein-Barr Virus Tegument Protein BNRF1.
abstract: It is now well established that several cellular proteins that are components of promyelocytic leukemia nuclear bodies (PML NBs, also known as ND10) have restrictive effects on herpesvirus infections that are countered by viral proteins that are either present in the virion particle or are expressed during the earliest stages of infection. For example, herpes simplex virus 1 (HSV-1) immediate early (IE) protein ICP0 overcomes the restrictive effects of PML-NB components PML, Sp100, hDaxx, and ATRX while human cytomegalovirus (HCMV) IE protein IE1 targets PML and Sp100, and its tegument protein pp71 targets hDaxx and ATRX. The functions of these viral regulatory proteins are in part interchangeable; thus, both IE1 and pp71 stimulate the replication of ICP0-null mutant HSV-1, while ICP0 increases plaque formation by pp71-deficient HCMV. Here, we extend these studies by examining proteins that are expressed by Epstein-Barr virus (EBV). We report that EBV tegument protein BNRF1, discovered by other investigators to target the hDaxx/ATRX complex, increases the replication of both ICP0-null mutant HSV-1 and pp71-deficient HCMV. In addition, EBV protein EBNA-LP, which targets Sp100, also augments ICP0-null mutant HSV-1 replication. The combination of these two EBV regulatory proteins had a greater effect than each one individually. These findings reinforce the concept that disruption of the functions of PML-NB proteins is important for efficient herpesvirus infections.
  
  
  OBJECTIVE
  Whether a herpesvirus initiates a lytic infection in a host cell or establishes quiescence or latency is influenced by events that occur soon after the viral genome has entered the host cell nucleus. Certain cellular proteins respond in a restrictive manner to the invading pathogen's DNA, while viral functions are expressed that counteract the cell-mediated repression. One aspect of cellular restriction of herpesvirus infections is mediated by components of nuclear structures known as PML nuclear bodies (PML NBs), or ND10. Members of the alpha-, beta-, and gammaherpesvirus families all express proteins that interact with, degrade, or otherwise counteract the inhibitory effects of various PML NB components. Previous work has shown that there is the potential for a functional interchange between the viral proteins expressed by alpha- and betaherpesviruses, despite a lack of obvious sequence similarity. Here, this concept is extended to include a member of the gammaherpesviruses.
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom.
authors.forename: Yongxu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Orr
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom roger.everett@glasgow.ac.uk.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Everett
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D034961:Antigens, Nuclear / Q000235:genetics; D001324:Autoantigens / Q000235:genetics; D002460:Cell Line; D056970:Co-Repressor Proteins; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D006561:Herpes Simplex / Q000235:genetics; D006566:Herpesviridae Infections / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D018832:Molecular Chaperones; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000071156:Promyelocytic Leukemia Protein / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*; D000075924:X-linked Nuclear Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D034961:Antigens, Nuclear; D001324:Autoantigens; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C402640:EBNA-LP protein, Human herpesvirus 4; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C062724:P140 protein, Epstein-barr virus; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C095533:gene 63 protein, Equine herpesvirus 1; C066642:SP100 protein, human; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein