title: Mechanisms of herpes simplex virus type 1 reactivation.
abstract: Primary cultures of trigeminal ganglion (TG) cells from herpes simplex virus type 1 (HSV-1) latently infected mice were used to study reactivation. Expression of HSV-1 latency-associated transcripts was noted in TG cell cultures. Infectious virus appeared in 75% of culture supernatants within 120 h after heat stress. Likewise, HSV-1 lytic-phase mRNA and proteins were detectable 24 h after heat stress. HSV-1 antigen first appeared in neurons after heat stress, indicating the neurons were the source of reactivation. The effect of heat stress duration on reactivation was determined. Reactivation occurred in 0, 40, or 67% of cultures after a 1-, 2-, or 3-h heat stress, respectively. However, 72-kDa heat shock protein expression was induced regardless of heat stress duration. Thus, reactivation was not a direct result of inducing the heat shock response. The capacities of several drugs to induce reactivation were also evaluated. While neither epinephrine, forskolin, nor a membrane-permeable cyclic AMP analog induced reactivation, dexamethasone did so in a dose-dependent manner. Furthermore, dexamethasone pretreatment enhanced the kinetics of heat stress-induced reactivation from TG cells. Collectively, the results indicate that TG cell cultures mimic important aspects of in vivo latency and reactivation. Therefore, this model may be useful for studying signalling pathways that lead to HSV-1 reactivation.
authors.affiliation: Department of Microbiology and Immunology, Louisiana State University Medical Center, New Orleans 70112, USA.
authors.forename: W P
authors.initials: WP
authors.lastname: Halford
authors.forename: B M
authors.initials: BM
authors.lastname: Gebhardt
authors.forename: D J
authors.initials: DJ
authors.lastname: Carr
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018882:Heat Stress Disorders; D006561:Herpes Simplex / Q000821:virology*; D051379:Mice; D012367:RNA, Viral / Q000378:metabolism; D018139:Simplexvirus / Q000254:growth & development* / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000821:virology*; D014764:Viral Proteins / Q000378:metabolism; D014775:Virus Activation
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins