A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. Much remains unknown regarding the cellular and viral mechanisms involved in HSV exit from latency. We hypothesize that VP16 recruits chromatin-remodeling enzymes to immediate early gene promoters on compact-latent chromatin as a necessary step for reactivation. In order to test this hypothesis, a robust in vitro assay in which HSV latency can be established in neurons was required. In this dissertation, I explored the use of a human sensory neuron cell line as a novel in vitro model of HSV-1 latency and reactivation. HD10.6 cells were derived from embryonic human dorsal root ganglia and immortalized by a tetracycline-regulated v-myc oncogene. HD10.6 cells mature to express a sensory neuron-associated phenotype when treated with doxycycline which suppresses proliferation mediated by the v-myc oncogene. Infection at a low MOI in the presence of acyclovir results in a quiescent infection resembling latency in matured cells. HD10.6 cells provide a novel context in which to study the host and viral mechanisms of HSV-1 latency establishment, maintenance, and reactivation.
|Commitee:||Bertke, Andrea, Brundin, Patrik, Duesbery, Nick, Kalejta, Robert|
|School:||Van Andel Research Institute|
|School Location:||United States -- Michigan|
|Source:||DAI-B 78/11(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Cellular biology, Virology|
|Keywords:||Alphaherpesviruses, Viral latency|
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