title: Early nucleosome deposition on, and replication of, HSV DNA requires cell factor PCNA.
abstract: Herpes simplex virus (HSV) is a double-stranded DNA virus that can cause lytic infections in epithelial cells of the skin and latent infections in neuronal cells of the peripheral nervous system. After virion attachment to the cell membrane, the capsid enters the cytoplasm and is transported to the nucleus. Following docking at the nuclear pore, the HSV DNA, and contents of the virion, are injected into the nucleus. The viral DNA that enters the nucleus is devoid of histones, but begins to be covered with them soon after entry. The covering of histones, in the form of nucleosomes, reaches a maximum during the early stages of infection and drops off during late infection (after DNA replication). However, during latency, the genome is saturated with nucleosomes. In this study, we examine the role of proliferating cell nuclear antigen (PCNA), a cellular DNA polymerase accessory protein (processivity factor), and cell DNA polymerases in histone deposition during the early stages of HSV infection. Using SiRNA knockdown, and a cytosine arabinoside (araC) chemical inhibitor, we conclude that PCNA is important for viral replication and histone deposition. However, cell DNA polymerases that bind PCNA do not appear to be required for these processes and PCNA does not appear to bind to the viral DNA polymerase (which has its own viral processivity factor).
authors: Department of Microbiology, University of Pennsylvania School of Medicine, 319 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA, 19104-6067, USA.
authors: Iryna
authors: I
authors: Sanders
authors: Mark
authors: M
authors: Boyer
authors: Nigel W
authors: NW
authors: Fraser
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D004279:DNA, Viral; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006790:Host-Parasite Interactions / Q000502:physiology*; D009707:Nucleosomes; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology*
chemical_list: D004279:DNA, Viral; D009707:Nucleosomes; D018809:Proliferating Cell Nuclear Antigen