Journal ArticleDOI
Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.
Michel Samson,Frédérick Libert,Benjamin J. Doranz,Joseph Rucker,Corinne Liesnard,Claire-Michèle Farber,Sentob Saragosti,Claudine Lapoumeroulie,Jacqueline Cognaux,Christine Forceille,Gaëtan Muyldermans,Chris Verhofstede,Guy Burtonboy,Michel Georges,Tsuneo Imai,Shalini Rana,Yanji Yi,Robert J. Smyth,Ronald G. Collman,Robert W. Doms,Gilbert Vassart,Marc Parmentier +21 more
TLDR
It is shown that a mutant allele of CCR-5 is present at a high frequency in caucasian populations, but is absent in black populations from Western and Central Africa and Japanese populations, and a 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains.Abstract:
HIV-1 and related viruses require co-receptors, in addition to CD4, to infect target cells. The chemokine receptor CCR-5 (ref.1) was recently demonstrated to be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains, and the orphan receptor LESTR (also called fusin) allows infection by strains adapted for growth in transformed T-cell lines (T-tropic strains). Here we show that a mutant allele of CCR-5 is present at a high frequency in caucasian populations (allele frequency, 0.092), but is absent in black populations from Western and Central Africa and Japanese populations. A 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains. In a cohort of HIV-1 infected caucasian subjects, no individual homozygous for the mutation was found, and the frequency of heterozygotes was 35% lower than in the general population. White blood cells from an individual homozygous for the null allele were found to be highly resistant to infection by M-tropic HIV-1 viruses, confirming that CCR-5 is the major co-receptor for primary HIV-1 strains. The lower frequency of heterozygotes in seropositive patients may indicate partial resistance.read more
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Chemokines — Chemotactic Cytokines That Mediate Inflammation
TL;DR: This review introduces the burgeoning family of cytokines, with special emphasis on their role in the pathophysiology of disease and their potential as targets for therapy.
Journal ArticleDOI
Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene
Michael Dean,Mary Carrington,Cheryl A. Winkler,Gavin A. Huttley,Michael W. Smith,Rando Allikmets,James J. Goedert,Susan Buchbinder,Eric Vittinghoff,Edward D. Gomperts,Sharyne Donfield,David Vlahov,Richard A. Kaslow,Alfred J. Saah,Charles R. Rinaldo,Roger Detels,Stephen J. O'Brien +16 more
TL;DR: The CKR5Δ32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.
Journal ArticleDOI
The biology of chemokines and their receptors.
Devora L. Rossi,Albert Zlotnik +1 more
TL;DR: Some of the chemokines' biological effects in vivo and in vitro, described in the last few years are discussed, and the implications of these findings when considering chemokine receptors as therapeutic targets are discussed.
Journal ArticleDOI
CHEMOKINE RECEPTORS AS HIV-1 CORECEPTORS: Roles in Viral Entry, Tropism, and Disease
TL;DR: In this paper, the chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophagetropic HIV-1 isolates, respectively.
Journal Article
International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors
Philip M. Murphy,Marco Baggiolini,Israel F. Charo,Caroline A. Hébert,Richard Horuk,Kouji Matsushima,Louis H. Miller,Joost J. Oppenheim,Christine A. Power +8 more
TL;DR: A widely accepted receptor nomenclature system is described, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area and updating current concepts of the biology and pharmacology of the chemokine system.
References
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Journal ArticleDOI
HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor
TL;DR: A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy that is a putative G protein-coupled receptor with seven transmembrane segments.
Journal ArticleDOI
Identification of a major co-receptor for primary isolates of HIV-1
Hongkui Deng,Rong Liu,Wilfried Ellmeier,S Choe,Derya Unutmaz,M Burkhart,P Di Marzio,Shoshana Marmon,R E Sutton,C M Hill,C B Davis,S C Peiper,T J Schall,Dan R. Littman,Nathaniel R. Landau +14 more
TL;DR: The principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR-5, a receptor for the β-chemokines RANTES, Mip-1α and MIP-1β.
Journal ArticleDOI
HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5.
Tatjana Dragic,Virginia M. Litwin,Graham P. Allaway,Scott R. Martin,Yaoxing Huang,Kirsten A. Nagashima,Charmagne Cayanan,Paul J. Maddon,Richard A. Koup,John P. Moore,William A. Paxton +10 more
TL;DR: The β-chemokine receptor CC-CKR-5 as mentioned in this paper is a second receptor for NSI primary viruses, which allows env-mediated cell-cell membrane fusion, but it does not allow the fusion of cells from some HIV-1-exposed uninfected individuals.
Journal ArticleDOI
Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells
Fiorenza Cocchi,Anthony L. DeVico,Alfredo Garzino-Demo,Suresh K. Arya,Robert C. Gallo,Paolo Lusso +5 more
TL;DR: Recombinant human RANTES, Mip-1α, and MIP-1β induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) and may have relevance for the prevention and therapy of AIDS.
Journal ArticleDOI
CC CKR5: A RANTES, MIP-1α, MIP-1β Receptor as a Fusion Cofactor for Macrophage-Tropic HIV-1
Ghalib Alkhatib,Christophe Combadiere,Christopher C. Broder,Yu Feng,Paul E. Kennedy,Philip Murphy,Edward A. Berger +6 more
TL;DR: Recombinant CC CKR5, a G protein-coupled receptor for these chemokines, rendered CD4-expressing nonhuman cells fusion-competent preferentially with macrophage-tropic Envs, and is thus a fusion cofactor for HIV-1 strains.