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
Schneider, Johann W; Dittmer, Dirk P (2017) Diagnosis and Treatment of Kaposi Sarcoma. Am J Clin Dermatol 18:529-539
Ma, Zhe; Hopcraft, Sharon E; Yang, Fan et al. (2017) NLRX1 negatively modulates type I IFN to facilitate KSHV reactivation from latency. PLoS Pathog 13:e1006350
Dittmer, Dirk P; Krown, Susan E; Mitsuyasu, Ronald (2017) Exclusion of Kaposi Sarcoma From Analysis of Cancer Burden. JAMA Oncol 3:1429
Schifano, Jason M; Corcoran, Kathleen; Kelkar, Hemant et al. (2017) Expression of the Antisense-to-Latency Transcript Long Noncoding RNA in Kaposi's Sarcoma-Associated Herpesvirus. J Virol 91:
Raab-Traub, Nancy; Dittmer, Dirk P (2017) Viral effects on the content and function of extracellular vesicles. Nat Rev Microbiol 15:559-572
Corcoran, Kathleen; Sherrod, Carly J; Perkowski, Ellen F et al. (2017) Genome Sequences of Diverse Human Cytomegalovirus Strains with Utility in Drug Screening and Vaccine Evaluation. Genome Announc 5:
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; Tamburro, Kristen; Chen, Huichao et al. (2017) Oral shedding of herpesviruses in HIV-infected patients with varying degrees of immune status. AIDS 31:2077-2084
Shiboski, C H; Webster-Cyriaque, J Y; Ghannoum, M et al. (2016) The Oral HIV/AIDS Research Alliance Program: lessons learned and future directions. Oral Dis 22 Suppl 1:128-34
McVoy, Michael A; Wang, Jian Ben; Dittmer, Dirk P et al. (2016) Repair of a Mutation Disrupting the Guinea Pig Cytomegalovirus Pentameric Complex Acquired during Fibroblast Passage Restores Pathogenesis in Immune-Suppressed Guinea Pigs and in the Context of Congenital Infection. J Virol 90:7715-27

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