Current therapies for human immunodeficiency virus type 1 (HIV-1) do not completely eliminate viral reservoirs in cells, such as macrophages. The HIV-1 accessory protein viral protein R (Vpr) promotes virus production in macrophages, and the maintenance of Vpr is essential for HIV-1 replication in these reservoir cells. We identified two novel Vpr-binding proteins, i.e., protein arginine N-methyltransferases (PRMTs) 5 and 7, using human monocyte-derived macrophages (MDMs). Both proteins found to be important for prevention of Vpr degradation by the proteasome; in the context of PRMT5 and PRMT7 knockdowns, degradation of Vpr could be prevented using a proteasome inhibitor. In MDMs infected with a wild-type strain, knockdown of PRMT5/PRMT7 and low expression of PRMT5 resulted in inefficient virus production like Vpr-deficient strain infections. Thus, our findings suggest that PRMT5 and PRMT7 support HIV-1 replication via maintenance of Vpr protein stability.

中文翻译：

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蛋白精氨酸N-甲基转移酶5和7促进HIV-1的产生。

当前针对人类1型免疫缺陷病毒（HIV-1）的疗法不能完全消除细胞（例如巨噬细胞）中的病毒库。HIV-1辅助蛋白病毒蛋白R（Vpr）促进巨噬细胞中病毒的产生，而Vpr的维持对于这些储存细胞中HIV-1的复制至关重要。我们使用人类单核细胞衍生的巨噬细胞（MDM）鉴定了两个新颖的Vpr结合蛋白，即蛋白精氨酸N-甲基转移酶（PRMTs）5和7。发现这两种蛋白对于防止蛋白酶体降解Vpr都很重要。在PRMT5和PRMT7敲低的情况下，可以使用蛋白酶体抑制剂防止Vpr降解。在感染了野生型毒株的MDM中，PRMT5 / PRMT7的敲低和PRMT5的低表达导致病毒生产效率低下，如Vpr缺陷型毒株感染。从而，