Journal ArticleDOI
Influence of CCR5 promoter haplotypes on AIDS progression in African-Americans.
Ping An,Maureen P. Martin,George W. Nelson,Mary Carrington,Michael W. Smith,Kui Gong,David Vlahov,Stephen J. O'Brien,Cheryl A. Winkler +8 more
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TLDR
The composite CCR5P1 haplotype is shown to be associated with rapid progression to AIDS endpoints in both African–American and Caucasian cohorts, but the effect is recessive in Caucasians and dominant in African–Americans.Abstract:
Objectives: To test the hypothesis that the CCR5 promoter variants in HIV-1-infected African-Americans affect the rate of progression to AIDS and to determine the extent of linkage disequilibrium between the CCR5P1 allele and the CCR5 59029A variant (referred to here as CCR5-2459A), both of which have been shown independently to accelerate AIDS progression in Caucasians. Design: We used survival analysis to assess the effects of CCR5 promoter variants in HIV-1 seroincident Caucasians and African-Americans. Subjects and methods: Genotypes were determined for 806 Caucasians and 1067 African-Americans, which included 700 seroconverters, enrolled in four HIV/AIDS natural history cohort studies. These genotypes were used to determine linkage and haplotypes for CCR2 and CCR5 alleles. Survival analysis was used to assess the effect of CCR2, CCR5, and CCR5 promoter haplotypes on progression to AIDS in seroincident African-Americans. Results: A survey of Caucasians and African-Americans demonstrated complete linkage disequilibrium between CCR5P1 and CCR5-2459A sites. The composite CCR5P1 haplotype (including the CCR5-2459A allele) is shown to be associated with rapid progression to AIDS endpoints in both African-American and Caucasian cohorts, but the effect is recessive in Caucasians and dominant in African-Americans. This is probably due to the presence of modulating genes or as yet unidentified polymorphisms that may differ between racial groups.read more
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The CCR5 and CXCR4 coreceptors--central to understanding the transmission and pathogenesis of human immunodeficiency virus type 1 infection.
TL;DR: This review will discuss what is known, what is suspected, and what still remains obscure about the central role played by coreceptor expression and usage in the transmission and pathogenic consequences of human immunodeficiency virus type 1 (HIV-1) infection.
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The Genomics and Genetics of Human Infectious Disease Susceptibility
TL;DR: A highly polygenic basis for susceptibility to many common infectious diseases is indicated, with some emerging examples of interaction between variants of specific polymorphic host and pathogen genes.
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Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?
TL;DR: This review looks afresh at the epidemiological evidence that supports a role for genetics in susceptibility to infectious disease, examines the somewhat limited achievements to date, and discusses current advances in methodology and technology that will potentially lead to translational data in the future.
Journal ArticleDOI
R5 HIV productively infects langerhans cells, and infection levels are regulated by compound CCR5 polymorphisms
Tatsuyoshi Kawamura,Forrest Gulden,Makoto Sugaya,David T. McNamara,Debra L. Borris,Michael M. Lederman,Jan M. Orenstein,Peter A. Zimmerman,Andrew Blauvelt +8 more
TL;DR: Genetic susceptibility data in LCs parallel those of genetic susceptibility studies performed in cohorts of HIV-infected individuals and suggest that CCR5-mediated infection of LCs, and not capture of virus byLCs, provides a biologic basis for understanding certain aspects of host genetic susceptibility to initial HIV infection.
Journal ArticleDOI
Modulating influence on HIV/AIDS by interacting RANTES gene variants.
Ping An,George W. Nelson,Lihua Wang,Sharyne Donfield,James J. Goedert,John P. Phair,David Vlahov,Susan Buchbinder,William L. Farrar,William S. Modi,Stephen J. O'Brien,Cheryl A. Winkler +11 more
TL;DR: The diminished transcription of RANTES afforded by the In1.1C regulatory allele is consistent with increased HIV-1 spread in vivo, leading to accelerated progression to AIDS.
References
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Analysis of Survival Data
David Cox,D. Oakes +1 more
TL;DR: In this article, the authors give a concise account of the analysis of survival data, focusing on new theory on the relationship between survival factors and identified explanatory variables and conclude with bibliographic notes and further results that can be used for student exercises.
Journal ArticleDOI
Homozygous Defect in HIV-1 Coreceptor Accounts for Resistance of Some Multiply-Exposed Individuals to HIV-1 Infection
Rong Liu,William A. Paxton,Sunny Choe,Daniel Ceradini,Scott R. Martin,Richard Horuk,Marcy E. MacDonald,Heidi Stuhlmann,Richard A. Koup,Nathaniel R. Landau +9 more
TL;DR: A CKR-5 allele present in the human population appears to protect homozygous individuals from sexual transmission of HIV-1 and is suggested to provide a means of preventing or slowing disease progression.
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.
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
TL;DR: 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.
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.
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Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene
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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