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).
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.
|Schneider, Johann W; Dittmer, Dirk P (2017) Diagnosis and Treatment of Kaposi Sarcoma. Am J Clin Dermatol 18:529-539|
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|Dittmer, Dirk P; Krown, Susan E; Mitsuyasu, Ronald (2017) Exclusion of Kaposi Sarcoma From Analysis of Cancer Burden. JAMA Oncol 3:1429|
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|Raab-Traub, Nancy; Dittmer, Dirk P (2017) Viral effects on the content and function of extracellular vesicles. Nat Rev Microbiol 15:559-572|
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|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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