John David Hamilton

1) My laboratory is engaged in studies of viral latency using murine cytomegalovirus, a member of the family of beta-Herpes viruses. Of particular interest in our laboratory, has been the mechanisms of control of latent virus. This question is, we believe, a biologically very important one since it has direct and indirect implications for viral transmission, prevention and treatment of disease.

2) In experiments using reverse transcriptase PCR, we were able to detect immediate-early I transcripts at a level roughly 10-fold higher than that of viral genome, indicating that a significant fraction of latent virus is transcriptionally active. These findings may be indicative of an abortive infection in which transcription is limited to the immediate-early genes, or the result of a very low level persistent infection, or a transient reactivation of latent virus. To further assess the state of viral activity in latent infection we have tested the activity of monoclonal antibodies against putative latent viral proteins. We have further established the gene map location encoding one of these unique proteins and is found to be distinct from the immediate early genes. Further studies using immunohistochemistry indicate that this viral gene is active during latency although not exclusively and therefore not likely to be a regulatory gene for latency. Presently using a recombinant virus containing the gene for green fluorescent protein we will attempt to localize the cellular reservoir latent virus by confocal microscopy.

3) In addition, I have been very active in the conduct of clinical trials relevant to HIV/AIDS. These include a study of early versus late AZT of which I was co-principal investigator in this VA Cooperative Study and I am principal investigator for a pending application to the NIH for an Adult AIDS Clinical Trials Network.

4) I am both a frequent reviewer of manuscripts submitted for publication in the general area of basic and clinical virology and I have been appointed to several national advisory committees including White House Task Force on HIV Vaccine (FCCSET), the Medical Research Advisory Committee of the Department of Veterans Affairs, and the FDA Antiviral Advisory Committee.

5) Key Words
Virus, latency, molecular, cytomegalovirus, immunocompromised, HIV, hepatitis