Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Curr Opin Virol. 2016 Aug;19:65-70. doi: 10.1016/j.coviro.2016.06.014. Epub 2016 Jul 21.
Evolutionary pressure has produced an 'arms race' between cellular restriction factors (limiting viral replication) and viral proteins (overcoming host restriction). The host factors SAMHD1 and SLFN1 patrol metabolic bottlenecks required for HIV replication. Conversely, the HIV accessory proteins Vpx, Vpu and Nef manipulate cellular metabolism to enable viral replication. Recent work identifying Vpu-mediated downregulation of the alanine transporter SNAT1 and Nef-mediated downregulation of the serine carriers SERINC3/5 has uncovered the importance of HIV manipulation of the amino acid supply. Interference with CD4(+) T-cell amino acid metabolism suggests a novel paradigm of viral immunomodulation, and signposts fundamental aspects of lymphocyte biology.
进化压力导致细胞限制因子（限制病毒复制）和病毒蛋白（克服宿主限制）之间产生了一场“军备竞赛”。宿主因子 SAMHD1 和 SLFN1 可以检测到 HIV 复制所需的代谢瓶颈。相反，HIV 的辅助蛋白 Vpx、Vpu 和 Nef 可以操纵细胞代谢，从而使病毒复制。最近的研究发现，Vpu 下调了丙氨酸转运蛋白 SNAT1，Nef 下调了丝氨酸载体 SERINC3/5，这揭示了 HIV 对氨基酸供应的操纵的重要性。干扰 CD4(+)T 细胞的氨基酸代谢提示了一种新型的病毒免疫调节模式，并为淋巴细胞生物学的基本方面提供了重要线索。
