title: Oligomerization of ICP4 and rearrangement of heat shock proteins may be important for herpes simplex virus type 1 prereplicative site formation.
abstract: Herpes simplex virus type 1 (HSV-1) DNA replication occurs in replication compartments that form in the nucleus by an ordered process involving a series of protein scaffold intermediates. Following entry of viral genomes into the nucleus, nucleoprotein complexes containing ICP4 can be detected at a position adjacent to nuclear domain 10 (ND10)-like bodies. ND10s are then disrupted by the viral E3 ubiquitin ligase ICP0. We have previously reported that after the dissociation of ND10-like bodies, ICP8 could be observed in a diffuse staining pattern; however, using more sensitive staining methods, we now report that in addition to diffuse staining, ICP8 can be detected in tiny foci adjacent to ICP4 foci. ICP8 microfoci contain UL9 and components of the helicase-primase complex. HSV infection also results in the reorganization of the heat shock cognate protein 70 (Hsc70) and the 20S proteasome into virus-induced chaperone-enriched (VICE) domains. In this report we show that VICE domains are distinct but adjacent to the ICP4 nucleoprotein complexes and the ICP8 microfoci. In cells infected with an ICP4 mutant virus encoding a mutant protein that cannot oligomerize on DNA, ICP8 microfoci are not detected; however, VICE domains could still be formed. These results suggest that oligomerization of ICP4 on viral DNA may be essential for the formation of ICP8 microfoci but not for the reorganization of host cell chaperones into VICE domains.
authors.affiliation: Department of Molecular, Microbial and Structural Biology, The University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Livingston
authors.forename: Neal A
authors.initials: NA
authors.lastname: DeLuca
authors.forename: Dianna E
authors.initials: DE
authors.lastname: Wilkinson
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Weller
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism* / Q000502:physiology; D017874:Immediate-Early Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; C045462:ICP8 protein, Simplexvirus; D017874:Immediate-Early Proteins; D014764:Viral Proteins; C048925:herpes simplex virus, type 1 protein ICP4