Liu Yu, Meng Feng-Zhen, Wang Xu, Wang Peng, Liu Jin-Biao, Hu Wen-Hui, Young Won-Bin, Ho Wen-Zhe
Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, 3500 N Broad St., Philadelphia, PA, 19140, USA.
Center for Substance Abuse Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Cell Biosci. 2021 Nov 10;11(1):194. doi: 10.1186/s13578-021-00703-4.
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.
甲基苯丙胺（METH）是一种强效成瘾性精神兴奋剂，在感染HIV的个体中高度流行。临床上，使用METH与免疫系统改变以及HIV传播/复制增加有关。因此，研究METH是否对单核细胞（该病毒的主要靶细胞和储存细胞）的HIV感染有直接影响具有重要意义。
METH处理的单核细胞对HIV感染更敏感，病毒蛋白（p24和Pr55Gag）水平升高以及病毒GAG基因表达增加证明了这一点。此外，使用带有荧光素酶报告基因的HIV Bal（HIV Bal-eLuc），我们发现METH处理的细胞比未处理的单核细胞表达更高的荧光素酶活性。从机制上讲，METH抑制IFN-λ1、IRF7、STAT1以及抗病毒IFN刺激基因（ISGs：OAS2、GBP5、ISG56、Viperin和ISG15）的表达。此外，METH下调HIV限制微小RNA（miR-28、miR-29a、miR-125b、miR-146a、miR-155、miR-223和miR-382）的表达。
METH损害细胞内抗HIV免疫并促进HIV在原代人单核细胞中的复制。
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