Recurrent herpes simplex virus (HSV) infections afflict millions of Americans producing significant physical and psychological morbidity, serving as an important source of communicable virus, and causing potentially life-threatening disease in the immunocompromised patient. Recurrent infections result from the reactivation is limited, with most research having focused on HSV type 1. The objective of this proposal is to explore the molecular events associated with HSV type 2 latency, reactivation and recurrence. The proposed research will use an experimental genital HSV infection of guinea pigs which has proven to be a unique self-limited vaginitis, latent infection of sensory ganglia, and both spontaneous and inducible recurrent disease. Polymerase chain reaction amplification and in situ hybridization will be used to characterize HSV-1 and HSV-2 transcription in latently infected sensory ganglia. The pattern of transcription will be correlated with the ability of the virus type to produce recurrent disease. Recently, UV irradiation has been shown to predictably induce recurrent genital herpes in latently infected guinea pigs. This model will be used to explore the molecular events associated with the reactivation of latent virus by using Northern blot/in situ hybridization and a genetically engineered HSV-2 mutant expressing the lac Z gene under the control of a late gene promoter. A limited region of the HSV-1 genome is transcribed during latent infection however, mutants deleted of this region are still capable of establishing and maintaining a latent infection. By ascertaining if such mutants can produce spontaneous and/or induced recurrent genital herpes in guinea pigs it will be possible to explore whether latency associated transcripts are important in the produce recurrent genital infections will be explored using intertypic HSV-1 X HSV-2 mutants. Molecular analyses of these mutants will define the regions of the HSV-2 genome responsible for recurrent genital herpes. The long term goal of this proposal is to expand our understanding of the pathophysiology of latent and recurrent HSV infections which will ultimately lead to new strategies for the control of an exceedingly common public health problem.
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