LATENT VIRUS INFECTION AND REACTIVATION

Project: Research project

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 date7/1/845/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $150,980.00
  • National Institutes of Health
  • National Institutes of Health

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Virus Diseases
Thymidine Kinase
Simplexvirus
Virus Latency
Human Herpesvirus 1
Viruses
In Situ Hybridization
Infection
Neurons
RNA
Ganglia