Mechanisms of expression of HHV8, EBV and HPV in selected HIV-associated oral lesions.

Abstract

Opportunistic DNA viruses, particularly members of the herpesvirus family, are frequently the aetiological agents of HIV-associated oral lesions. Oral lesions common to the early phase of the AIDS epidemic, including Kaposi's sarcoma (KS), oral aphthous ulceration, AIDS-associated oral lymphoma, and oral hairy leukoplakia (OHL), have been tested for the prevalence of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). While EBV DNA is detected by PCR in all of these lesions, abundant viral replication can only be detected in OHL. In OHL, a novel state of EBV infection has been discovered with concurrent expression of replicative and transforming proteins, with all of these proteins contributing to the development of the lesion. Activation of signalling pathways and up-regulation of the viral receptor, proliferative and antiapoptotic genes by these proteins induce several of the histological features common to OHL, such as acanthosis and hyperproliferation. In contrast to other permissive herpesvirus infections, expression of EBV transforming proteins within the permissively infected OHL tissue enables epithelial cell survival and may enhance viral replication. Detection of KSHV in these HIV-infected individuals has been localized only to their saliva. Replicative and latent KSHV gene products have been detected in association with the development of oral KS lesions. EBV, but not human cytomegalovirus (HCMV), has been detected by PCR in minor salivary gland biopsies of HIV-associated salivary gland disease. Human papillomaviruses (HPV) are associated with oral warts in HIV-positive individuals; a diagnosis that appears to be increasing in frequency in the era of highly active antiretroviral therapy. To date, there appears to be little increase in the incidence of HPV-associated oral cancer. The mechanisms of interaction between HIV and HPV are not fully understood. Expression of viral gene products is clearly important and necessary for the development of multiple AIDS-associated oral lesions.