Methamphetamine facilitates HIV infection of primary human monocytes through inhibiting cellular viral restriction factors.
Methamphetamine facilitates HIV infection of primary human monocytes through inhibiting cellular viral restriction factors.
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DOI：
10.1186/s13578-021-00703-4
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发表时间：
2021-11-10
影响因子：
7.5
通讯作者：
Ho WZ
中科院分区：
文献类型：
--
作者：
Liu Y;Meng FZ;Wang X;Wang P;Liu JB;Hu WH;Young WB;Ho WZ
甲基苯丙胺(冰毒)是一种有效的成瘾精神刺激剂，在艾滋病毒感染者中非常普遍。在临床上，冰毒的使用涉及免疫系统的改变和艾滋病毒传播/复制的增加。因此，研究冰毒是否对单核细胞的HIV感染有直接作用具有重要意义。单核细胞是HIV病毒的主要靶细胞和储存细胞。病毒蛋白(p24和Pr55Gag)水平和病毒Gag基因表达增加表明，经冰毒处理的单核细胞对HIV感染更敏感。此外，利用带有荧光素酶报告基因的HIV Bal-eLuc(HIV Bal-eLuc)，我们发现甲基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。在机制上，METH可抑制干扰素-λ1、IRF7、STAT1和抗病毒刺激基因(ISGs：OAS2、GbP5、ISG56、Viperin和ISG15)的表达。此外，METH还下调了HIV限制性microRNAs(miR-28、miR-29a、miR-125b、miR-146a、miR-155、miR-223和miR-382)的表达。METH损害了细胞内的抗HIV免疫，并促进了HIV在原代人类单核细胞中的复制。网上版载有补充材料，可在10.1186/s13578-021-00703-4查阅。
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. The online version contains supplementary material available at 10.1186/s13578-021-00703-4.