Rawat Satinder S, Johnson Benitra T, Puri Anu
Laboratory of Experimental and Computational Biology, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, P.O. Box B, Bldg. 469, Rm. 211, Miller Drive, Frederick, MD 21702, USA.
Biosci Rep. 2005 Oct-Dec;25(5-6):329-43. doi: 10.1007/s10540-005-2894-5.
HIV-1 infects host cells by sequential interactions of its fusion protein (gp120-gp41) with receptors CD4, CXCR4 and/or CCR5 followed by fusion of viral and host membranes. Studies indicate that additional factors such as receptor density and composition of viral and cellular lipids can dramatically modulate the fusion reaction. Lipid rafts, which primarily consist of sphingolipids and cholesterol, have been implicated for infectious route of HIV-1 entry. Plasma membrane Glycosphingolipids (GSLs) have been proposed to support HIV-1 infection in multiple ways: (a) as alternate receptor(s) for CD4-independent entry in neuronal and other cell types, (b) viral transmission, and (c) gp120-gp41-mediated membrane fusion. However, the exact mechanism(s) by which GSLs support fusion is still elusive. This article will focus on the contribution of target membrane sphingolipids and their metabolites in modulating viral entry. We will discuss the current working hypotheses underlying the mechanisms by which these lipids promote and/or block HIV-1 entry. Recent approaches in the design and development of novel glycosyl derivatives, as anti-HIV agents will be summarized.
HIV-1通过其融合蛋白（gp120-gp41）与受体CD4、CXCR4和/或CCR5的顺序相互作用感染宿主细胞，随后病毒膜与宿主膜融合。研究表明，其他因素如受体密度以及病毒和细胞脂质的组成可显著调节融合反应。主要由鞘脂和胆固醇组成的脂筏与HIV-1进入的感染途径有关。质膜糖鞘脂（GSLs）被认为以多种方式支持HIV-1感染：（a）作为神经元和其他细胞类型中不依赖CD4进入的替代受体，（b）病毒传播，以及（c）gp120-gp41介导的膜融合。然而，GSLs支持融合的确切机制仍不清楚。本文将重点关注靶膜鞘脂及其代谢产物在调节病毒进入中的作用。我们将讨论这些脂质促进和/或阻断HIV-1进入机制的当前工作假说。作为抗HIV药物的新型糖基衍生物设计和开发的最新方法将被总结。
