Association of the cellular coactivator HCF-1 with the Golgi apparatus in sensory neurons.
HCF-1 is a cellular transcriptional coactivator that is critical for mediating the regulated expression of the immediate-early genes of the alphaherpesviruses herpes simplex virus type 1 and varicella-zoster virus. HCF-1 functions, at least in part, by modulating the modification of nucleosomes at these viral promoters to reverse cell-mediated repressive marks and promote activating marks. Strikingly, HCF-1 is specifically sequestered in the cytoplasm of sensory neurons where these viruses establish latency and is rapidly relocalized to the nucleus upon stimuli that result in viral reactivation. However, the analysis of HCF-1 in latently infected neurons and the protein's specific subcellular location have not been determined. Therefore, in this study, the localization of HCF-1 in unstimulated and induced latently infected sensory neurons was investigated and was found to be similar to that observed in uninfected mice, with a time course of induced nuclear accumulation that correlated with viral reactivation. Using a primary neuronal cell culture system, HCF-1 was localized to the Golgi apparatus in unstimulated neurons, a unique location for a transcriptional coactivator. Upon disruption of the Golgi body, HCF-1 was rapidly relocalized to the nucleus in contrast to other Golgi apparatus-associated proteins. The location of HCF-1 is distinct from that of CREB3, an endoplasmic reticulum-resident HCF-1 interaction partner that has been proposed to sequester HCF-1. The results support the model that HCF-1 is an important component of the viral latency-reactivation cycle and that it is regulated by association with a component that is distinct from the identified HCF-1 interaction factors.
Kolb
Gaelle
G
National Institutes of Health, 4-129, 4 Center Drive, Bethesda, MD 20892, USA.
Kristie
Thomas M
TM
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein; D015967:Gene Expression Regulation, Viral; D006056:Golgi Apparatus / Q000378:metabolism*; D051863:Host Cell Factor C1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013347:Subcellular Fractions; D013997:Time Factors
D002843:Chromatin; C116472:Creb3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1