PMID: 9420225Jan 7, 1998Paper

Amino-terminal substitutions in the CCR5 coreceptor impair gp120 binding and human immunodeficiency virus type 1 entry

Journal of Virology
T DragicP J Maddon

Abstract

The CC-chemokine receptor CCR5 is required for the efficient fusion of macrophage (M)-tropic human immunodeficiency virus type 1 (HIV-1) strains with the plasma membrane of CD4+ cells and interacts directly with the viral surface glycoprotein gp120. Although receptor chimera studies have provided useful information, the domains of CCR5 that function for HIV-1 entry, including the site of gp120 interaction, have not been unambiguously identified. Here, we use site-directed, alanine-scanning mutagenesis of CCR5 to show that substitutions of the negatively charged aspartic acid residues at positions 2 and 11 (D2A and D11A) and a glutamic acid residue at position 18 (E18A), individually or in combination, impair or abolish CCR5-mediated HIV-1 entry for the ADA and JR-FL M-tropic strains and the DH123 dual-tropic strain. These mutations also impair Env-mediated membrane fusion and the gp120-CCR5 interaction. Of these three residues, only D11 is necessary for CC-chemokine-mediated inhibition of HIV-1 entry, which is, however, also dependent on other extracellular CCR5 residues. Thus, the gp120 and CC-chemokine binding sites on CCR5 are only partially overlapping, and the former site requires negatively charged residues in the amino-t...Continue Reading

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Citations

Jul 17, 1999·The Journal of Peptide Research : Official Journal of the American Peptide Society·M MoulardJ M Sabatier
Sep 5, 2001·Journal of Virology·F BaribaudR W Doms
Jul 18, 2001·The Journal of General Virology·T Dragic
Feb 28, 2002·Journal of Virology·Daniah A D ThompsonTatjana Dragic
Aug 17, 2002·The Journal of Biological Chemistry·Michael FarzanHyeryun Choe
May 21, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alain MechulamFrancisco Veas
Apr 27, 2005·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Liying MaCorinne Capoulade-Métay
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Dec 7, 2005·Antiviral Chemistry & Chemotherapy·Mike Westby, Elna van der Ryst
Nov 1, 2007·The Journal of Biological Chemistry·Kazuaki MondeKeisuke Yusa
Sep 10, 2011·AIDS Research and Human Retroviruses·Maria Espirito-SantoJ Miguel Azevedo-Pereira
Jun 8, 1999·Annual Review of Immunology·E A BergerJ M Farber
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·E G CormierT Dragic
Mar 13, 2001·Annual Review of Immunology·P PoignardD R Burton
Jul 3, 2003·The Journal of Biological Chemistry·Diana Alvarez AriasStephen C Peiper
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·T DragicJ P Moore
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Sep 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michelle S TengJohn McCafferty

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