Yu Liu1, Feng-Zhen Meng1, Xu Wang1,2, Peng Wang1,2, Jin-Biao Liu1, Wen-Hui Hu1, Won-Bin Young1, Wen-Zhe Ho1,2. 1. Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, 3500 N Broad St., Philadelphia, PA 19140 USA. 2. Center for Substance Abuse Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140 USA.
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. Results: METH-treated monocytes were more susceptible to HIV infection as evidenced by increased levels of viral proteins (p24 and Pr55Gag) and expression of viral GAG gene. In addition, using HIV Bal with luciferase reporter gene (HIV Bal-eLuc), we showed that METH-treated cells expressed higher luciferase activities than untreated monocytes. Mechanistically, METH inhibited the expression of IFN-λ1, IRF7, STAT1, and the antiviral IFN-stimulated genes (ISGs: OAS2, GBP5, ISG56, Viperin and ISG15). In addition, METH down-regulated the expression of the HIV restriction microRNAs (miR-28, miR-29a, miR-125b, miR-146a, miR-155, miR-223, and miR-382). Conclusions: METH compromises the intracellular anti-HIV immunity and facilitates HIV replication in primary human monocytes. Supplementary Information: The online version contains supplementary material available at 10.1186/s13578-021-00703-4.
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. Results: METH-treated monocytes were more susceptible to HIV infection as evidenced by increased levels of viral proteins (p24 and Pr55Gag) and expression of viral GAG gene. In addition, using HIV Bal with luciferase reporter gene (HIV Bal-eLuc), we showed that METH-treated cells expressed higher luciferase activities than untreated monocytes. Mechanistically, METH inhibited the expression of IFN-λ1, IRF7, STAT1, and the antiviral IFN-stimulated genes (ISGs: OAS2, GBP5, ISG56, Viperin and ISG15). In addition, METH down-regulated the expression of the HIV restriction microRNAs (miR-28, miR-29a, miR-125b, miR-146a, miR-155, miR-223, and miR-382). Conclusions: METH compromises the intracellular anti-HIV immunity and facilitates HIV replication in primary human monocytes. Supplementary Information: The online version contains supplementary material available at 10.1186/s13578-021-00703-4.
Authors: Christian Krapp; Dominik Hotter; Ali Gawanbacht; Paul J McLaren; Silvia F Kluge; Christina M Stürzel; Katharina Mack; Elisabeth Reith; Susanne Engelhart; Angela Ciuffi; Veit Hornung; Daniel Sauter; Amalio Telenti; Frank Kirchhoff Journal: Cell Host Microbe Date: 2016-03-17 Impact factor: 21.023