An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence.

An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence. Research Abstract Details 

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An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence. Abstract Text:

Human immunodeficiency virus (HIV) type 1 infection requires functional interactions of the viral surface (gp120) glycoprotein with cell surface CD4 and a chemokine coreceptor (usually CCR5 or CXCR4) and of the viral transmembrane (gp41) glycoprotein with the target cell membrane. Extensive genetic variability, generally in gp120 and the gp41 ectodomain, can result in altered coreceptor use, fusion kinetics, and neutralization sensitivity. Here we describe an R5 HIV variant that, in contrast to its parental virus, infects T-cell lines expressing low levels of cell surface CCR5. This correlated with an ability to infect cells in the absence of CD4, increased sensitivity to a neutralizing antibody recognizing the coreceptor binding site of gp120, and increased resistance to the fusion inhibitor T-20. Surprisingly, these properties were determined by alterations in gp41, including the cytoplasmic tail, a region not previously shown to influence coreceptor use. These data indicate that HIV infection of cells with limiting levels of cell surface CCR5 can be facilitated by gp41 sequences that are not exposed on the envelope ectodomain yet induce allosteric changes in gp120 that facilitate exposure of the CCR5 binding site.

An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence. Publishing Authors By Initials

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An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of virology

VOLUME: 82

Page Numbers: 5460-71

Journal Abbreviation: J. Virol.

ISSN: 1098-5514

DAY: 19

MONTH: 03

YEAR: 2008

An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence. Information

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LANGUAGE: eng

NlmUniqueID: 113724

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Grant and Affiliation Information for An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence.

AFFILIATION: Institute of Human Virology, School of Medicine, and Department of Microbiology and Immunology, University of Maryland Baltimore, 725 W. Lombard St., Baltimore, Maryland 21201, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL59796

ACRONYM: HL

MEDLINETA: J Virol

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