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CCL3L1

About: CCL3L1 is a research topic. Over the lifetime, 27 publications have been published within this topic receiving 7134 citations. The topic is also known as: 464.2 & D17S1718.

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Journal ArticleDOI
22 Aug 1996-Nature
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.
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.

2,668 citations

Journal ArticleDOI
27 Sep 1996-Science
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.
Abstract: The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4 + T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele ( CKR5Δ32 ) was identified that is present at a frequency of ∼0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. 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.

2,586 citations

Journal ArticleDOI
04 Mar 2005-Science
TL;DR: It is shown that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1, a potent human immunodeficiency virus–1 (HIV-1)–suppressive chemokine and ligand for the HIV coreceptor CCR5.
Abstract: Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1αP), a potent human immunodeficiency virus–1 (HIV-1)–suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.

1,205 citations

Journal ArticleDOI
TL;DR: In this article, the authors measured CCL3L1 copy-number in 1136 RA cases from New Zealand (NZ) and the UK, 252 NZ T1D cases and a total of 1470 controls.
Abstract: Objective: There is increasing evidence that gene copy-number variation influences phenotypic variation. Chemokine ligand 3-like 1 ( CCL3L1 ) is encoded by a variable copy-number gene, and binds to several pro-inflammatory cytokine receptors, including chemokine receptor 5 (CCR5). Considering lymphocyte recruitment by β-chemokines is a feature of autoimmunity, and that the CCR5Δ32 variant is associated with protection to rheumatoid arthritis (RA), we hypothesised that CCL3L1 copy-number influences susceptibility to RA and type 1 diabetes (T1D). Methods: We measured CCL3L1 copy-number in 1136 RA cases from New Zealand (NZ) and the UK, 252 NZ T1D cases and a total of 1470 controls. All subjects were ancestrally Caucasian. Results: A copy-number higher than 2 (the most common copy number) was a risk factor for RA in the NZ cohort (odds ratio (OR) 1.34, 95% CI 1.08–1.66, p = 0.009) but not the smaller UK RA cohort (OR 1.09, 95% CI 0.75–1.60, p = 0.643). There was evidence for association in the T1D cohort (OR 1.46, 95% CI 0.98–2.20, p = 0.064) and in the combined RA/T1D cohort (OR 1.30, 95% CI 1.00–1.54, p = 0.003). Genetic interaction between CCL3L1 dosage and CCR5 genotype was found; the increased genetic risk conferred by higher CCL3L1 copy-number was ablated by a dysfunctional CCR5 ( CCR5 Δ 32 ). Conclusions: These data suggest that increased CCL3L1 expression may enhance inflammatory responses and increase the chance of autoimmune disease. Genetic interaction data were consistent with a biologically plausible model; CCR5 Δ 32 protects against RA and T1D by blocking signalling through the CCR5 pathway, mitigating the pro-inflammatory effects of excess CCL3L1.

176 citations

Journal ArticleDOI
TL;DR: It is demonstrated that a proline residue at position 2 of MIP-1αP is responsible for enhanced receptor binding affinities to CCR5 and the promiscuous β-chemokine receptor, D6, and suggests that Mip-1 αP may be of importance in controlling viral spread in HIV-infected individuals.

135 citations

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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20201
20191
20171
20141
20121
20111