Varicella-zoster virus immediate-early 63 protein interacts with human antisilencing function 1 protein and alters its ability to bind histones h3.1 and h3.3.
Varicella-zoster virus (VZV) immediate-early 63 protein (IE63) is abundantly expressed during both acute infection in vitro and latent infection in human ganglia. Using the yeast two-hybrid system, we found that VZV IE63 interacts with human antisilencing function 1 protein (ASF1). ASF1 is a nucleosome assembly factor which is a member of the H3/H4 family of histone chaperones. IE63 coimmunoprecipitated and colocalized with ASF1 in transfected cells expressing IE63 and in VZV-infected cells. IE63 also colocalized with ASF1 in both lytic and latently VZV-infected enteric neurons. ASF1 exists in two isoforms, ASF1a and ASF1b, in mammalian cells. IE63 preferentially bound to ASF1a, and the amino-terminal 30 amino acids of ASF1a were critical for its interaction with IE63. VZV IE63 amino acids 171 to 208 and putative phosphorylation sites of IE63, both of which are critical for virus replication and latency in rodents, were important for the interaction of IE63 with ASF1. Finally, we found that IE63 increased the binding of ASF1 to histone H3.1 and H3.3, which suggests that IE63 may help to regulate levels of histones in virus-infected cells. Since ASF1 mediates eviction and deposition of histones during transcription, the interaction of VZV IE63 with ASF1 may help to regulate transcription of viral or cellular genes during lytic and/or latent infection.
Ambagala
Aruna P
AP
Laboratory of Clinical Infectious Diseases, National Institutes of Health, 10 Center Dr., Building 10, Room 11N234, Bethesda, MD 20892, USA. jcohen@niaid.nih.gov
Bosma
Trent
T
Ali
Mir A
MA
Poustovoitov
Maxim
M
Chen
Jason J
JJ
Gershon
Michael D
MD
Adams
Peter D
PD
Cohen
Jeffrey I
JI
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D005724:Ganglia / Q000737:chemistry / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006168:Guinea Pigs; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D008297:Male; D018613:Microscopy, Confocal; D018832:Molecular Chaperones; D009474:Neurons / Q000737:chemistry / Q000821:virology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020798:Two-Hybrid System Techniques; D014759:Viral Envelope Proteins / Q000378:metabolism*; D017735:Virus Latency; D014779:Virus Replication
C491641:ASF1A protein, human; D018797:Cell Cycle Proteins; D006657:Histones; D017874:Immediate-Early Proteins; D018832:Molecular Chaperones; D014759:Viral Envelope Proteins; C074551:immediate early protein 63, Human herpesvirus 3