Oral biology of the Kaposi's sarcoma-associated herpesvirus

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Kaposi's sarcoma (KS) associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is associated with malignancies, especially in immune suppressed patients including those with AIDS. KSHV is tightly linked to KS, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD), an aggressive lymphoproliferative disorder. KSHV infection in tumors and PEL cell lines is predominantly latent, with viral DNA persisting as a multicopy episome. KSHV expresses a limited number of genes in patent infection and the program of latent gene expression varies in different malignancies. Lytic KSHV infection occurs in a small percentage of cells in both tumors and PEL cell lines. Although epidemiological data indicates that KSHV is transmitted both sexually among men who have sex with men and also non sexually, its specific mode of transmission remains to be elucidated. Oral transmission have been implicated for KSHV and could account for both sexual and non sexual routes of infection. Consistent with oral transmission,, high levels of KSHV DNA are found in saliva but not semen, prostatic secretions or stool. Further, saliva contains infectious KSHV since virus could be transmitted in vitro to 293 cells. The high levels of KSHV DNA in saliva suggest that lytic infection may have a more prominent role in the oral cavity than in KSHV associated tumors. Of note, in vivo KSHV infection has recently been shown in superficial keratinocytes scraped from the oral mucosa of patients. However, a detailed analysis of KSHV latent and lytic infection in the oropharyngeal cavity remains to be performed. This work will investigate the biology of KSHV in the oropharyngeal cavity. Site(s) of KSHV infection will be identified and the nature of the infection at each site will be determined. Cell types infected with KSHV will be defined and patterns of both latent and lytic KSHV gene expression within different cell types will be determined. In addition, an in vitro system of KSHV infection of primary oral keratinocytes will be developed. Such a system should facilitate future investigations of KSHV oropharyngeal infection.