KS is a vascular tumor caused by infection with KSHV. The oropharynx plays a central role in KSHV infection. KSHV transmission occurs through saliva which, in sub-Saharan Africa, occurs at high rates beginning in eariy childhood. KSHV replication Is detected most frequently in the oral cavity, and oral viral replication is strongly associated with viremia. Therefore, understanding the biology and pathogenesis of oral KSHV infection appears critical to devising strategies to interrupt transmission and prevent spread throughout the host. This Clinical Core will enroll cohorts and collect biological specimens to support the Program Project, "Oral pathogenesis and host interactions of Kaposi sarcoma-associated herpesvirus (KSHV) infection" (PI Dr. Timothy Rose). The goal of the Clinical Core is to foster innovative translational research on KSHV infection, replication, pathogenesis and immunity through the collection of uniquely valuable biological specimens from KSHV-infected people in an area hyperendemic for KS. Cohorts will be enrolled at the Uganda Cancer Institute (UCI) in Kampala, Uganda through our outstanding collaborative research group, the Uganda Program on Cancer and Infectious Disease (UPCID). The Clinical Core will be responsible for the enrollment, evaluation, and follow-up of clinical cohorts at the UCI, and for obtaining and managing laboratory specimens for all four projects of this RFA.
Aim 1 of the Clinical Core is to recruit, screen, and enroll KSHV-infected children and adults into research protocols in Kampala, Uganda. Study participants will be enrolled into studies by experienced UPCID research staff. Follow-up of participants will be performed in accordance with the ethical conduct of human subjects research, using proven methods to maximize adherence to study procedures.
Aim 2 is to collect, process, and ship clinical specimens suitable for the study of;(1) KSHV infection of oral epithelial and lymphoid cells using oral tissue collected from routine tonsillectomies;(2) expression of phenotypic markers of angiogenesis and lymphatic differentiation in oral and cutaneous KS tumor biopsies;and (3) immune correlates of the control of KSHV infection using saliva and blood specimens collected from HIV-infected and uninfected subiects followed at the UCI.
KS is the most common malignancy among HIV-infected people worldwide. Most of the population in Uganda and other areas of sub-Saharan Africa are infected with KSHV. In these regions, where HIV infection is also highly prevalent, KS ranks among the most common cancers of adults and children in the general population.
|Bruce, A Gregory; Horst, Jeremy A; Rose, Timothy M (2016) Conservation of the glycoprotein B homologs of the Kaposi×³s sarcoma-associated herpesvirus (KSHV/HHV8) and old world primate rhadinoviruses of chimpanzees and macaques. Virology 494:29-46|
|DiMaio, Terri A; Wentz, Breanna L; Lagunoff, Michael (2016) Isolation and characterization of circulating lymphatic endothelial colony forming cells. Exp Cell Res 340:159-69|
|Lagunoff, Michael (2016) Activation of cellular metabolism during latent Kaposi's Sarcoma herpesvirus infection. Curr Opin Virol 19:45-9|
|Sanchez, Erica L; Lagunoff, Michael (2015) Viral activation of cellular metabolism. Virology 479-480:609-18|
|Fontaine, Krystal A; Sanchez, Erica L; Camarda, Roman et al. (2015) Dengue virus induces and requires glycolysis for optimal replication. J Virol 89:2358-66|
|Bruce, A Gregory; Thouless, Margaret E; Haines, Anthony S et al. (2015) Complete genome sequence of Pig-tailed macaque rhadinovirus 2 and its evolutionary relationship with rhesus macaque rhadinovirus and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus. J Virol 89:3888-909|
|DiMaio, Terri A; Gutierrez, Kimberley D; Lagunoff, Michael (2014) Kaposi's sarcoma-associated herpesvirus downregulates transforming growth factor Î²2 to promote enhanced stability of capillary-like tube formation. J Virol 88:14301-9|
|Fontaine, Krystal A; Camarda, Roman; Lagunoff, Michael (2014) Vaccinia virus requires glutamine but not glucose for efficient replication. J Virol 88:4366-74|
|Staheli, Jeannette P; Dyen, Michael R; Lewis, Patrick et al. (2014) Discovery and biological characterization of two novel pig-tailed macaque homologs of HHV-6 and HHV-7. Virology 471-473:126-40|
|Stockinger, Diane E; Fong, Derek L; Vogel, Keith W et al. (2014) Oral squamous cell carcinoma in a pigtailed macaque (Macaca nemestrina). Comp Med 64:234-9|
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