Methamphetamine Facilitates HIV Infection of Human Monocytes Through Inhibiting Cellular Viral Restriction Factors

Abstract

Background Methamphetamine (METH), a potent addictive psychostimulant, is highly prevalent in HIV-infected individuals. Clinically, METH use is implicated in alteration of immune system and increase of HIV spread/replication. Therefore, it is of importance to examine whether METH has direct effect on HIV infection of monocytes, the major target and reservoir cells for the virus. Result METH-treated monocytes were more susceptible to HIV infection as evidenced by increased levels of viral p24 protein and expression of viral GAG gene. Mechanistically, METH treatment of monocytes inhibited the expression of the antiviral IFN-stimulated genes (ISGs: OAS2, GBP5, ISG56, Viperin and ISG15) and the HIV restriction microRNAs. In addition, METH treatment of monocytes significantly decreased STAT1 expression at both mRNA and protein levels. Conclusions These findings suggest a previously unrecognized mechanism for HIV persistent infection in the primary target and reservoir cells.