Methamphetamine facilitates HIV infection of primary human monocytes through inhibiting cellular viral restriction factors

Springer Science and Business Media LLC - Tập 11 - Trang 1-9 - 2021
Yu Liu1, Feng-Zhen Meng1, Xu Wang1,2, Peng Wang1,2, Jin-Biao Liu1, Wen-Hui Hu1, Won-Bin Young1, Wen-Zhe Ho1,2
1Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, USA
2Center for Substance Abuse Research, Temple University Lewis Katz School of Medicine, Philadelphia, USA

Tóm tắt

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. 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). METH compromises the intracellular anti-HIV immunity and facilitates HIV replication in primary human monocytes.

Tài liệu tham khảo

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