Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia; Current affiliation: RIKEN Cluster for Pioneering Research and RIKEN Center for Integrative Medical Sciences, 1-chōme-7-22 Suehirochō, Tsurumi-ku, Yokohama 230-0045, Kanagawa, Japan.
School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria 3083, Australia.
Trends Microbiol. 2023 Apr;31(4):393-404. doi: 10.1016/j.tim.2022.11.001. Epub 2022 Nov 30.
Antiretroviral therapy (ART) reduces human immunodeficiency virus type 1 (HIV-1) infection, but selection of treatment-refractory variants remains a major challenge. HIV-1 encodes 16 canonical proteins, a small number of which are the singular targets of nearly all antiretrovirals developed to date. Cellular factors are increasingly being explored, which may present more therapeutic targets, more effectively target certain aspects of the viral replication cycle, and/or limit viral escape. Unlike most other positive-sense RNA viruses that encode at least one helicase, retroviruses are limited to the host repertoire. Accordingly, HIV-1 subverts DEAD-box helicase 3X (DDX3X) and numerous other cellular helicases of the Asp-Glu-x-Asp/His (DExD/H)-box family to service multiple aspects of its replication cycle. Here we review DDX3X and other DExD/H-box helicases in HIV-1 replication and their inhibition.
抗逆转录病毒疗法（ART）可降低人类免疫缺陷病毒 1 型（HIV-1）感染，但治疗耐药变体的选择仍然是一个主要挑战。HIV-1 编码 16 种规范蛋白，其中少数是迄今为止开发的几乎所有抗逆转录病毒药物的单一靶点。细胞因子正越来越多地被探索，这可能提供更多的治疗靶点，更有效地针对病毒复制周期的某些方面，和/或限制病毒逃逸。与大多数其他编码至少一种解旋酶的正链 RNA 病毒不同，逆转录病毒仅限于宿主基因库。因此，HIV-1 会劫持 DEAD-box 解旋酶 3X（DDX3X）和其他许多细胞解旋酶的 Asp-Glu-x-Asp/His（DExD/H）盒家族，以服务于其复制周期的多个方面。在这里，我们综述了 DDX3X 和 HIV-1 复制过程中的其他 DExD/H 盒解旋酶及其抑制作用。
