Department of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China.
School of science, University of Management and Technology, Lahore, Pakistan.
Front Immunol. 2024 Aug 16;15:1390650. doi: 10.3389/fimmu.2024.1390650. eCollection 2024.
Different host proteins target different HIV proteins and antagonize their functions, depending on the stage of the HIV life cycle and the stage of infection. Concurrently, HIV proteins also target and antagonize various different host proteins to facilitate HIV replication within host cells. The preceding quite specific area of knowledge in HIV pathogenesis, however, remains insufficiently understood. We therefore propose, in this review article, to examine and discuss the HIV proteins that counteract those host restriction proteins which results directly in increased infectivity of HIV. We elaborate on HIV proteins that antagonize host cellular proteins to promote HIV replication, and thus HIV infection. We examine the functions and mechanisms via which Nef, Vif, Vpu, Env, Vpr, and Vpx counteract host proteins such as Ser5, PSGL-1, IFITMS, A3G, tetherin, GBP5, SAMHD1, STING, HUSH, REAF, and TET2 to increase HIV infectivity. Nef antagonizes three host proteins, viz., Ser5, PSGL1, and IFITIMs, while Vpx also antagonizes three host restriction factors, viz., SAMHD1, STING, and HUSH complex; therefore, these proteins may be potential candidates for therapeutic intervention in HIV infection. Tetherin is targeted by Vpu and Env, PSGL1 is targeted by Nef and Vpu, while Ser5 is targeted by Nef and Env proteins. Finally, conclusive remarks and future perspectives are also presented.
不同的宿主蛋白针对不同的 HIV 蛋白，并根据 HIV 生命周期和感染阶段拮抗其功能。同时，HIV 蛋白也针对和拮抗各种不同的宿主蛋白，以促进 HIV 在宿主细胞内的复制。然而，HIV 发病机制中前面提到的非常具体的知识领域仍然理解不足。因此，在这篇综述文章中，我们提出研究和讨论拮抗宿主限制蛋白的 HIV 蛋白，这直接导致 HIV 感染性增加。我们详细阐述了拮抗宿主细胞蛋白以促进 HIV 复制从而促进 HIV 感染的 HIV 蛋白。我们研究了 Nef、Vif、Vpu、Env、Vpr 和 Vpx 通过何种功能和机制拮抗 Ser5、PSGL-1、IFITMS、A3G、tetherin、GBP5、SAMHD1、STING、HUSH、REAF 和 TET2 等宿主蛋白，以增加 HIV 的感染性。Nef 拮抗三种宿主蛋白，即 Ser5、PSGL1 和 IFITIMs，而 Vpx 也拮抗三种宿主限制因子，即 SAMHD1、STING 和 HUSH 复合物；因此，这些蛋白可能是 HIV 感染治疗干预的潜在候选物。Tetherin 被 Vpu 和 Env 靶向，PSGL1 被 Nef 和 Vpu 靶向，而 Ser5 则被 Nef 和 Env 蛋白靶向。最后，还提出了结论性意见和未来展望。
