Today the majority of human immune deficiency virus (HIV) infected patients in the US are on long-term (10+ years) antiretroviral therapy (ART). While ART suppresses HIV replication to below 50 copies / ml, not much is known about the long-term effect of these ART drugs on Kaposi sarcoma associated herpesvirus (KSHV) transmission and disease. We hypothesize that ART drug exposure contributes directly to a restriction in KSHV gene expression. If so, the mechanism could manifest itself in epigenetic modification of the viral episome and in altered release of micro RNAs in salivary exosomes. Such modification may respond differently to different drug regimens. Currently no other experimental studies investigate KSHV pathobiology in the background of multi-year exposure to ART drugs. This is a renewal application in response to PA-10- 290/Research on Malignancies in the Context of HIV/AIDS (R01).

Public Health Relevance

This application seeks to understand how anti-retroviral therapy drugs modulate AIDS associated oral infections and cancer. It seeks to validate novel biomarkers in saliva and oral samples. We base our approach on a novel class of RNAs, the so-called micro RNAs, that has been detected in oral secretions and that we and others have shown to correlate with different stages of tumor progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE018304-07
Application #
8734371
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Rodriguez-Chavez, Isaac R
Project Start
2007-05-15
Project End
2018-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Selitsky, Sara R; Marron, David; Mose, Lisle E et al. (2018) Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality. mSystems 3:
Hosseinipour, Mina C; Kang, Minhee; Krown, Susan E et al. (2018) As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial. Clin Infect Dis 67:251-260
Bigi, Rachele; Landis, Justin T; An, Hyowon et al. (2018) Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A 115:E11379-E11387
Hopcraft, Sharon E; Pattenden, Samantha G; James, Lindsey I et al. (2018) Chromatin remodeling controls Kaposi's sarcoma-associated herpesvirus reactivation from latency. PLoS Pathog 14:e1007267
Sin, Sang-Hoon; Eason, Anthony B; Bigi, Rachele et al. (2018) Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Renders B Cells Hyperresponsive to Secondary Infections. J Virol 92:
Zhang, Yugen; Dittmer, Dirk P; Mieczkowski, Piotr A et al. (2018) RIG-I Detects Kaposi's Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner. MBio 9:
Lee, Jennifer S; Cole, Stephen R; Achenbach, Chad J et al. (2018) Cancer risk in HIV patients with incomplete viral suppression after initiation of antiretroviral therapy. PLoS One 13:e0197665
Host, Kurtis M; Jacobs, Sarah R; West, John A et al. (2017) Kaposi's Sarcoma-Associated Herpesvirus Increases PD-L1 and Proinflammatory Cytokine Expression in Human Monocytes. MBio 8:
Angius, Fabrizio; Piras, Enrica; Uda, Sabrina et al. (2017) Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation. J Antibiot (Tokyo) 70:962-966
Dittmer, Dirk P; Krown, Susan E; Mitsuyasu, Ronald (2017) Exclusion of Kaposi Sarcoma From Analysis of Cancer Burden. JAMA Oncol 3:1429

Showing the most recent 10 out of 74 publications