title: Caspase-3-dependent reactivation of latent herpes simplex virus type 1 in sensory neuronal cultures.
abstract: Life-long latent herpes simplex virus type 1 (HSV-1) is harbored in sensory neurons where sporadic reactivation occurs. Reactivation stimuli may involve activation of apoptotic signaling in the neuron. Previous experiments have demonstrated that reactivation of latent HSV-1 in dorsal root ganglion (DRG) neuronal cultures occurred following nerve growth factor (NGF) deprivation. NGF deprivation stimulates apoptotic signaling by activating the proapoptotic proteolytic enzyme, caspase-3. When DRG neuronal cultures harboring latent HSV-1 were treated with a caspase-3-specific inhibitor, NGF deprivation-induced reactivation was significantly reduced. Interestingly, the caspase-3 inhibitor had no effect on productive HSV-1 infection. Furthermore, activation of caspase-3 with either C2-ceramide or a recombinant adenovirus expressing caspase-3 caused significant HSV-1 reactivation.
authors.affiliation: Department of Microbiology, Colorado State University, Fort Collins, Colorado, USA. enh4@cdc.gov
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hunsperger
authors.forename: Christine L
authors.initials: CL
authors.lastname: Wilcox
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D002478:Cells, Cultured / Q000201:enzymology / Q000821:virology; D005576:Colforsin / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D005727:Ganglia, Spinal / Q000166:cytology / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009475:Neurons, Afferent / Q000201:enzymology / Q000821:virology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects; D017735:Virus Latency
chemical_list: D015853:Cysteine Proteinase Inhibitors; C064769:N-acetylsphingosine; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C108637:aspartyl-glutamyl-valyl-aspartal; D005576:Colforsin; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate