In people living with HIV/AIDS, viral proteins (Nef/Rev), anti-retroviral therapy and drugs of abuse activate Epstein-Barr virus latency genes in correlation with the expression of MEF-2 oncogenes 2041

Abstract Description The latent cycle of EBV regulates the development of EBV-associated lymphomas in people living with HIV/AIDS (PLWH). Herein, we investigated the effects of various factors, which can impact EBV latency in PLWH in cooperation with the cellular oncoproteins such as myocyte enhancer factor (MEF)-2 family. Most individuals infected with HIV are on antiretroviral therapy (ART), which is not able to eradicate HIV or cure the infection. The prolonged ART use and consistent presence of soluble HIV proteins impose health risks, including an accelerated course of many cancers. Similarly, oncogenesis is prevalent among substance users. However, the exact mechanisms linking drugs of abuse and cancer remain unclear. Herein, we treated EBV-infected lymphoblastoid cell lines with soluble HIV proteins (Nef, Rev, etc.), ART and various substances of abuse to evaluate the expression of EBV genes, as well as cancer-promoting MEF-2 genes (A-D). We observed that soluble Nef, Rev, and ART as well as cocaine, morphine, and methamphetamine, promote the expression of EBV genes linked to oncogenesis and MEF-2 isoforms (A/C) supporting the connection between HIV, substance abuse, and cancer. Validation of these results in clinical samples is underway along with the analysis of underlying mechanisms. These findings establish a clear link between oncogenesis and persistent HIV infection, prolonged use of ART and drugs of abuse, highlighting the potential oncogenic risks for these HIV-associated factors. Funding Sources Interconsortium Pilot Funding from the Sydney Kimmel Cencer Center, a NCI accredited cancer facility in Philadelphia, PA, USA. Topic Categories Viral Immunology (VIR)