Once an individual is infected with herpes simplex virus (HSV), the virus establishes a latent infection in sensory neurons. Periodically, various stimuli may induce lytic reactivation resulting in mild recurrent lesions to more severe disease. The factors which determine the establishment of latency and reactivation are poorly understood. However, considering the requirements for the viral IE gene products in productive infection, it is likely that the regulation of this latency-reactivation cycle is dependent upon the components which regulate the expression of the IE genes. The critical component of this regulatory process is HCF-1. Analyses of this protein in a mouse model have shown that the protein is specifically sequestered in the cytoplasm of sensory neurons and rapidly transported to the nucleus in response to reativation stimuli. Recent work has resulted in the establishment of a primary sensory neuronal cell culture which allowed for the specific localization of HCF-1 in the cytoplasm. Additional studies have determined that the nuclear transport of HCF-1 in latently infected neurons correlates with viral reactivation and that HCF-1 is rapidly recruited to the promoters of the viral IE genes upon initiation of reactivation. Finally, data suggests that HCF-1 modulates viral chromatin structure to initiate viral reactivation from latency. The data support the model whereby HCF-1 represents a critical switch component for viral reactivation.

Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2010
Total Cost
$346,368
Indirect Cost
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State
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