Sphingolipids, cholesterol, and HIV-1: A paradigm in viral fusion |
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Authors: | Satinder Singh Rawat Mathias Viard Stephen A Gallo Robert Blumenthal Anu Puri |
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Institution: | (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 |
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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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Keywords: | Viral entry Cholesterol Sphingolipids Membrane fusion HIV-1 |
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