A prospective on drug abuse-associated epigenetics and HIV-1 replication

Abstract

Drugs of abuse serve as cofactors to susceptibility to HIV infection and disease progression. Although clinical reports indicate association between HIV/AIDS and drug use, the molecular mechanism of infection susceptibility and disease progression remains unclear. Drugs such as cocaine exert their addictive effects in part by epigenetic mechanisms. Given that epigenetic modifications play an important role in HIV-1 life cycle, it is essential to unravel whether drug abuse-associated epigenetic changes may contribute to HIV/AIDS. In this article we will provide a prospective on the impact of epigenetic mechanisms on HIV-1 life cycle.

Figure 1

Overview of HIV-1 lifecycle as described by D’Souza and Summers 2005. The HIV-1 genome encodes nine open reading frames. Three of these encode the Gag, Pol, and Env polyproteins. Gag consists of MA (matrix), CA (capsid), NC (nucleocapsid), and p6 proteins. The two Env proteins; SU (surface or gp120) and TM (transmembrane or gp41), along with the Gag proteins make up the virion core and outer membrane envelope. The three Pol proteins; PR (protease), RT (reverse transcriptase), and IN (integrase) provide essential enzymatic functions and are also encapsulated within the particle. HIV-1 encodes six additional accessory proteins, three of which (Vif, Vpr, and Nef) are found in the viral particle. Two other accessory proteins, Tat and Rev, provide essential gene regulatory functions, and the last protein, Vpu, assists in assembly of the virion. Two genomic RNA molecules of ~ 9 kb are also packaged in the particle.

Figure 2

Schematics of retroviral integration as per Craigie, et al. The pre-integration complex (PIC) enters the nucleus via nuclear pore complex (NPC). The PIC gains access to chromatin and viral DNA is integrated by IN.