RRC ID 42100
Author Rawat SS, Eaton J, Gallo SA, Martin TD, Ablan S, Ratnayake S, Viard M, KewalRamani VN, Wang JM, Blumenthal R, Puri A.
Title Functional expression of CD4, CXCR4, and CCR5 in glycosphingolipid-deficient mouse melanoma GM95 cells and susceptibility to HIV-1 envelope glycoprotein-triggered membrane fusion.
Journal Virology
Abstract We had previously reported that glycosphingolipids (GSL) support human immunodeficiency virus type 1 (HIV-1) entry. In this study, we further examined this issue by expressing HIV-1 receptors in GSL-deficient GM95 cells. GM95 cells expressing low levels of CD4 and CXCR4 or CCR5 did not support HIV-1 Env-mediated fusion. However, higher expression of these receptors rendered GM95 cells highly susceptible to fusion with cells expressing appropriate HIV-1 envelope glycoproteins (HIV-1 Envs). The GM95 cells exhibited a different fusion phenotype when compared with GSL(+) NIH3T3 cells bearing similar receptor levels. Fusion of GM95 targets expressing higher levels of CD4 and coreceptors occurred at 25 degrees C and was sensitive to cholesterol depletion or disruption of the cytoskeleton. In contrast, the fusion threshold of NIH3T3CD4X4/R5 targets was at >/=28 degrees C as previously reported and was insensitive to cholesterol depletion or cytoskeletal network disruption. On the basis of these observations, we propose that target membrane GSLs support HIV-1 Env-mediated fusion at low density of receptors by stabilizing receptor pools in natural targets.
Volume 318(1)
Pages 55-65
Published 2004-1-5
DOI 10.1016/j.virol.2003.08.042
PII S0042682203006639
PMID 14972535
MeSH Animals CD4 Antigens / metabolism* Gene Products, env / pharmacology* Glycosphingolipids / deficiency* Glycosphingolipids / metabolism HIV-1 / pathogenicity HIV-2 / pathogenicity HeLa Cells Humans Melanoma Membrane Fusion / drug effects* Mice NIH 3T3 Cells Receptors, CCR5 / metabolism* Receptors, CXCR4 / metabolism* Tumor Cells, Cultured
IF 2.819
Times Cited 17
WOS Category VIROLOGY
Resource
Human and Animal Cells GM95(RCB1026)