Jay C. Brown, PhD

Jay C. Brown, PhD

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Herpes viruses and cancer etiology and treatment (Chemotherapy side effects, Lyphoma)

For cancer patients, herpesviruses are important both as the cause of particular malignancies and as opportunistic pathogens in patients undergoing treatment for cancer. Epstein-Barr virus (EBV), for instance, is involved in the etiology of Burkitt's lymphoma, nasopharyngeal carcinoma and probably several additional lymphomas. Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a skin lesion. Herpesviruses involved in opportunistic infections of cancer patients include herpes simplex virus (HSV) and human cytomegalovirus (HCMV). Both can cause keritoconjunctivitis, gastrointestinal illness, encephalitis and disseminated infections, with immunosuppressed patients at particular risk.

The Brown lab study herpesvirus infections that affect cancer patients with emphasis on HSV-1 and KSHV. In both cases, the goal is to examine the structure and assembly of the virus capsid with the idea that such studies will suggest the nature of novel anti-herpes therapeutic agents directed against capsid assembly. Although most of the studies are carried out with HSV-1 and KSHV, it is expected that the results will clarify capsid assembly as it occurs in other herpes viruses and perhaps in other virus families as well.

Studies in the laboratory have defined the basic steps involved in capsid formation. Using an in vitro assembly system, they have recently clarified the way the portal becomes incorporated into capsids as they are assembled. The assembly project has led to the identification of an inhibitor of HSV-1 replication, WAY-150138, that acts by antagonizing incorporation of the portal as the capsid is formed. The lab is now attempting to define the mechanism of WAY-150138 action more closely and determine whether it or related thiourea compounds may be useful for therapy against herpesvirus infections.