| Abstract |
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.
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