Sphingolipids: modulators of HIV-1 infection and pathogenesis.
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.
Rawat
Satinder S
SS
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.
Johnson
Benitra T
BT
Puri
Anu
A
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D044966:Anti-Retroviral Agents / Q000494:pharmacology; D015704:CD4 Antigens / Q000096:biosynthesis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002518:Ceramides / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D006028:Glycosphingolipids / Q000737:chemistry; D015658:HIV Infections / Q000473:pathology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D008956:Models, Chemical; D019713:Receptors, CCR5 / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000378:metabolism; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D015704:CD4 Antigens; D002518:Ceramides; D006023:Glycoproteins; D006028:Glycosphingolipids; D008055:Lipids; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D013107:Sphingolipids