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Sphingolipids, cholesterol, and HIV-1: A paradigm in viral fusion

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Abstract

Our previous studies show that the depletion of cholesterol or sphingolipids (raft-associated lipids) from receptor-bearing adherent cell lines blocks HIV-1 entry and HIV-1 Env-mediated membrane fusion. Here we have evaluated the mechanism(s) by which these lipids contribute to the HIV-1 Env-mediated membrane fusion. We report the following: (1) GSL depletion from a suspension T lymphocyte cell line (Sup-T1) reduced subsequent fusion with HIV-1IIIB-expressing cells by 70%. (2) Cholesterol depletion from NIH3T3 cells bearing HIV-1 receptors (NIH3T3CD4R5/NIH3T3CD4X4) did not impair subsequent fusion with HeLa cells expressing the corresponding HIV-1 Envs. In contrast GSL depletion from these targets reduced fusion by 50% suggesting that GSL facilitate fusion in different ways. (3) GSL-deficient GM95 cells bearing high receptors fused with HIV-1 Env-expressing cells at 37°C with kinetics similar to that of GSL + NIH3T3 targets. Based on these observations, we propose that the plasma membrane cholesterol is required to maintain the integrity of receptor pools whereas GSLs are involved in stabilizing the coupling of inter-receptor pools.

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Abbreviations

CT:

cholera toxin

GSL(s):

glycosphingolipid(s)

SM:

Sphingomyelin

MeβCD:

methyl β-cyclodextrin

HIV-1 Env-gp:

human immunodeficiency virus Type-1 Envelope Glycoprotein

HIV-1:

human immunodeficiency virus Type-1

DRMs:

detergent-resistant membrane domains

Lipid Rafts:

dynamic assemblies of lipids and proteins in the plasma membrane of cells enriched in sphingolipids and cholesterol, which are characterized by virtue of their insolubility in Triton X100 at 4°C also termed as detergent resistant membranes (DRM)

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Authors and Affiliations

  1. Laboratory of Experimental and Computational Biology, Center for Cancer Research NCI-Frederick, NIH, P.O. Box B, Bldg. 469, Rm. 211, Miller Drive Frederick, MD

    Satinder Singh Rawat, Mathias Viard, Stephen A. Gallo, Robert Blumenthal & Anu Puri

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  1. Satinder Singh Rawat
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  2. Mathias Viard
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  3. Stephen A. Gallo
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Correspondence to Anu Puri.

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Rawat, S.S., Viard, M., Gallo, S.A. et al. Sphingolipids, cholesterol, and HIV-1: A paradigm in viral fusion. Glycoconj J 23, 189–197 (2006). https://doi.org/10.1007/s10719-006-7924-4

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