LATENT VIRUS INFECTION AND REACTIVATION

  • Tenser, Richard (PI)

Project: Research project

Project Details

Description

Herpes simplex virus (HSV) latency has been well characterized as an infection of the human nervous system, usually of sensory ganglion neurons. Latent HSV infections are the substrate of recurrent HSV infections and possibly other illnesses as well. Mechanisms for the establishment of HSV latency and reactivation of infection in neurons are largely unknown. In order to establish HSV latency, it is likely that the lytic HSV cascade need be diminished. It is hypothesized that this may be achieved partially by neuron-specific transcription regulators. Similar factors are likely to be involved in the reactivation process in latently infected neurons, since it is improbable that many neurons are destroyed by reactivation, although infectious virus is synthesized. HSV latency will be investigated in newborn mice, after neurectomy and in ganglion transplants, situations which are expected to alter neuronal transcription mechanisms. HSV RNA transcription will be studied by in situ and blot hybridization. Similarly, cellular transcriptional regulators of potential importance in control of the lytic infection will be studied by these techniques. Newly developed ganglion transplantation techniques will be utilized to investigate the molecular pathogenesis of HSV latency in terms of host factors and pharmacological agents that may interfere with the establishment of latency. Lastly, we will evaluate the likely non-neuronal site of at least some HSV latency and the effect of HSV infection on ganglion neuron function in studies of neuropeptide expression. HSV infection clearly alters in vivo neuronal function, although this has been uncommonly studied. These investigations will provide insights to the molecular and cellular basis of HSV latency, as well as an understanding altered neuronal functioning which results from HSV infection.
StatusFinished
Effective start/end date7/1/855/31/95

Funding

  • National Institute of Neurological Disorders and Stroke: $158,954.00

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