Dr. Mudit Tyagi, recipient of a DC CFAR Pilot Award and Assistant Professor at the Department of Medicine at GW, collaborated on an article that was recently published in Virology. The article, entitled "Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-kB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR", provides detailed insights into cocaine-driven HIV-1 transcription and replication. The abstract can be found below.
Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication.