Kaposi' sarcoma (KS) is a vascular neoplasm associated with HIV infection and often manifests in the oral cavity. Infection of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), has been well established as the etiology of KS in the past decade. It has been shown that HIV infection modulates other viral infections via either direct HIV-virus interactions or alterations of host factors, including the immune system and cytokines. Several studies have also demonstrated KSHV infection and shedding in the oral cavity of HIV-infected subjects. The long-term goal of our research program is to understand the molecular mechanism of KSHV-induced pathogenesis, providing a scientific basis for preventive and therapeutic purposes. The objectiveof this application is to examine the molecular basis of interactions between HIV and KSHV in the oropharyngeal environments in order to test the central hypothesis that HIV infection alters oral environments, and as a result, modulates KSHV infection, latency and reactivation in the oral cavity.
Two specific aims will be pursued: 1) To examine the modulation of KSHV viral loads and genotypes by HIV infection in the oral cavity; and 2) To examine the modulation of KSHV latency and reactivation by HIV infection in the oral cavity. We have established an extensive track record in KSHV research, and have already developed various technologies and related reagents that are needed for this project. The proposed study is significant because it will define the biology and virology of HIV-KSHV interactions in the oral cavity, and potentially identify novel therapeutic targets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE017333-03
Application #
7257896
Study Section
Special Emphasis Panel (ZDE1-YL (13))
Program Officer
Rodriguez-Chavez, Isaac R
Project Start
2005-09-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$311,478
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Pediatrics
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
He, Meilan; Tan, Brandon; Vasan, Karthik et al. (2017) SIRT1 and AMPK pathways are essential for the proliferation and survival of primary effusion lymphoma cells. J Pathol 242:309-321
Li, W; Hu, M; Wang, C et al. (2017) A viral microRNA downregulates metastasis suppressor CD82 and induces cell invasion and angiogenesis by activating the c-Met signaling. Oncogene 36:5407-5420
Gruffaz, Marion; Vasan, Karthik; Tan, Brandon et al. (2017) TLR4-Mediated Inflammation Promotes KSHV-Induced Cellular Transformation and Tumorigenesis by Activating the STAT3 Pathway. Cancer Res 77:7094-7108
He, Meilan; Yuan, Hongfeng; Tan, Brandon et al. (2016) SIRT1-mediated downregulation of p27Kip1 is essential for overcoming contact inhibition of Kaposi's sarcoma-associated herpesvirus transformed cells. Oncotarget 7:75698-75711
Ye, Feng-Chun; Zhou, Fu-Chun; Nithianantham, Stanley et al. (2013) Kaposi's sarcoma-associated herpesvirus induces rapid release of angiopoietin-2 from endothelial cells. J Virol 87:6326-35
Zhang, Wei; Gao, Shou-Jiang (2012) Exploitation of Cellular Cytoskeletons and Signaling Pathways for Cell Entry by Kaposi's Sarcoma-Associated Herpesvirus and the Closely Related Rhesus Rhadinovirus. Pathogens 1:102-27
Fu, Bishi; Yang, Rongge; Xia, Fan et al. (2012) Gender differences in Kaposi's sarcoma-associated herpesvirus infection in a population with schistosomiasis in rural China. Jpn J Infect Dis 65:350-3
Ye, Fengchun; Lattif, Ali Abdul; Xie, Jianping et al. (2012) Nutlin-3 induces apoptosis, disrupts viral latency and inhibits expression of angiopoietin-2 in Kaposi sarcoma tumor cells. Cell Cycle 11:1393-9
Guadalupe, Moraima; Pollock, Brad H; Westbrook, Steven et al. (2011) Risk factors influencing antibody responses to Kaposi's sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy. J Acquir Immune Defic Syndr 56:83-90
Ye, Fengchun; Lei, Xiufen; Gao, Shou-Jiang (2011) Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation. Adv Virol 2011:

Showing the most recent 10 out of 33 publications