ArticleJournal of virology2004
Role for CCR5Delta32 protein in resistance to R5, R5X4, and X4 human immunodeficiency virus type 1 in primary CD4+ cells.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 104 citations in OpenAlex.
- Trial
- The chemokine receptor CCR5: multi-faceted hook for HIV-1.Retrovirology · 2024Review
- Low prevalence of HIV in the northern Cameroon: contribution of some AIDS restriction genes and potential implications for gene therapy.Frontiers in genetics · 2024Article
- Resistance to Human Immunodeficiency Virus 1 Infection Conferred by a Compound CCR5Δ32 and CCR5 C20S Heterozygote.The Journal of infectious diseases · 2023Article
- Article
- Multiplexed shRNA-miRs as a candidate for anti HIV-1 therapy: strategies, challenges, and future potential.Journal, genetic engineering & biotechnology · 2022Review
- The CD8Microbiology and molecular biology reviews : MMBR · 2021Review
- Genetically edited CD34Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Dual Role of CCR5 in the Course of Influenza Infection: Exploring Treatment Opportunities.Frontiers in immunology · 2021Review
- CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population.Frontiers in immunology · 2021Review
- CCR5 and Biological Complexity: The Need for Data Integration and Educational Materials to Address Genetic/Biological Reductionism at the Interface of Ethical, Legal, and Social Implications.Frontiers in immunology · 2021Article
- Review
- Prevalence of CCR5delta32 in Northeastern Iran.BMC medical genetics · 2019Article
- The technical risks of human gene editing.Human reproduction (Oxford, England) · 2019Article
- Predominance of the heterozygous CCR5 delta-24 deletion in African individuals resistant to HIV infection might be related to a defect in CCR5 addressing at the cell surface.Journal of the International AIDS Society · 2019Article
- Genetic Polymorphisms in the Open Reading Frame of the CCR5 gene From HIV-1 Seronegative and Seropositive Individuals From National Capital Regions of India.Scientific reports · 2019Article
- The potential risks of C-C chemokine receptor 5-edited babies in bone development.Bone research · 2019Review
- A guide to chemokines and their receptors.The FEBS journal · 2018Review
- Interaction of the Host and Viral Genome and Their Influence on HIV Disease.Frontiers in genetics · 2018Review
- A quantitative comparison of anti-HIV gene therapy delivered to hematopoietic stem cells versus CD4+ T cells.PLoS computational biology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
CCR5Delta32 is a loss-of-function mutation that abolishes cell surface expression of the human immunodeficiency virus (HIV) coreceptor CCR5 and provides genetic resistance to HIV infection and disease progression. Since CXCR4 and other HIV coreceptors also exist, we hypothesized that CCR5Delta32-mediated resistance may be due not only to the loss of CCR5 function but also to a gain-of-function mechanism, specifically the active inhibition of alternative coreceptors by the mutant CCR5Delta32 protein. Here we demonstrate that efficient expression of the CCR5Delta32 protein in primary CD4(+) cells by use of a recombinant adenovirus (Ad5/Delta32) was able to down-regulate surface expression of both wild-type CCR5 and CXCR4 and to confer broad resistance to R5, R5X4, and X4 HIV type 1 (HIV-1). This may be important clinically, since we found that CD4(+) cells purified from peripheral blood mononuclear cells of individuals who were homozygous for CCR5Delta32, which expressed the mutant protein endogenously, consistently expressed lower levels of CXCR4 and showed less susceptibility to X4 HIV-1 isolates than cells from individuals lacking the mutation. Moreover, CD4(+) cells from individuals who were homozygous for CCR5Delta32 expressed the mutant protein in five of five HIV-exposed, uninfected donors tested but not in either of two HIV-infected donors tested. The mechanism of inhibition may involve direct scavenging, since we were able to observe a direct interaction of CCR5 and CXCR4 with CCR5Delta32, both by genetic criteria using the yeast two-hybrid system and by biochemical criteria using the coimmunoprecipitation of heterodimers. Thus, these results suggest that at least two distinct mechanisms may account for genetic resistance to HIV conferred by CCR5Delta32: the loss of wild-type CCR5 surface expression and the generation of CCR5Delta32 protein, which functions as a scavenger of both CCR5 and CXCR4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.