Kaposi's sarcoma (KS) is one of the dominant opportunistic diseases associated with HIV, both in the United States and in the developing world. In the early 1980's, Baral and Jaffee suggested that KS appeared to be a sexually transmitted infection separate from HIV. In 1994, Chang and Moore detected a gamma herpes virus in biopsy tissue of patients with KS. This virus now called KSHV or HHV-8 has been shown to have worldwide prevalence and to be the etiologic agent of, endemic, African and HIV associated KS. HHV-8 has also been associated with multicentric Castleman's disease and Primary Lymphomatous effusions. While HHV-8 appears to be sexually transmitted among men who have sex with men (MSM), acquisition during early childhood is well documented, especially in parts of the world where the virus exists in high prevalence. Even among MSM, the mode of transmission of HHV-8 is unclear. Our group has had a long-standing interest in the biology and transmission of HHV-8. In a series of studies, we have shown that HHV-8 DNA is detected 10 times more frequently in oropharyngeal than genital secretions. Moreover, the titers of HHV-8 in mucosal pharyngeal swabs and saliva are 2-3 logs higher than semen, prostatic secretions and anal/rectal swabs. Saliva contains virion HHV-8, suggesting that direct contact with oral secretions is an important mechanism for HHV-8 transmission from seropositive men to their sex partners. However, little is known about the biology of oral infection, particularly the source of virus replication in the oropharynx and factors that determine frequency and concentrations of HHV-8 in saliva. The applicants' preliminary studies indicate that concentrations of HHV-8 in saliva are higher in individuals with concurrent HIV infection and that swabs from the tonsil and lingual surfaces appear to contain the highest titers of virus. Salivary glands do not appear to be the major sources of oropharyngeal virus. In a preliminary study, they obtained tonsil biopsies from 2 HHV-8/HIV seropositive men; both showed prominent infection of germinal center B lymphocytes in sites of HIV p24 antigen expression. HHV-8 lytic gene transcripts in these biopsies appear to localize to epithelial cells extending from the lymphoepithelial juncture to the capsular surface. This proposal is devoted to defining the pathogenesis of HHV-8 replication in the oropharynx. It describes a combination of in vitro studies using a novel recombinant virus to define the relationship between epithelial cell differentiation and HHV-8 infection and in vivo studies to define the anatomic sites and cellular localization of HHV-8 replication in the oropharynx.
| Barcy, Serge; De Rosa, Stephen C; Vieira, Jeffrey et al. (2008) Gamma delta+ T cells involvement in viral immune control of chronic human herpesvirus 8 infection. J Immunol 180:3417-25 |
| Johnson, Andrew S; Maronian, Nicole; Vieira, Jeffrey (2005) Activation of Kaposi's sarcoma-associated herpesvirus lytic gene expression during epithelial differentiation. J Virol 79:13769-77 |
| Ro, Jin Y; Nies, Michael; Zhang, Youping (2005) The role of peripheral N-methyl-D-aspartate receptors in muscle hyperalgesia. Neuroreport 16:485-9 |
| Vieira, Jeffrey; O'Hearn, Patricia M (2004) Use of the red fluorescent protein as a marker of Kaposi's sarcoma-associated herpesvirus lytic gene expression. Virology 325:225-40 |
| Lavreys, Ludo; Chohan, Bhavna; Ashley, Rhoda et al. (2003) Human herpesvirus 8: seroprevalence and correlates in prostitutes in Mombasa, Kenya. J Infect Dis 187:359-63 |
