ArticleProceedings of the National Academy of Sciences of the United States of America2002
Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
47 citing papers in PubMed, 115 citations in OpenAlex.
- CCR5 Receptor Occupancy Analysis Reveals Increased Peripheral Blood CCR5+CD4+ T Cells Following Treatment With the Anti-CCR5 Antibody Leronlimab.Frontiers in immunology · 2021Trial
- MRE11 and TREX1 control senescence by coordinating replication stress and interferon signaling.Nature communications · 2024Article
- The chemokine receptor CCR5: multi-faceted hook for HIV-1.Retrovirology · 2024Review
- Functional mapping of microRNA promoters with dCas9 fused to transcriptional regulators.Frontiers in genetics · 2023Article
- Article
- Identifying CCR5 coreceptor populations permissive for HIV-1 entry and productive infection: implications for in vivo studies.Journal of translational medicine · 2022Article
- CCR5 as a Coreceptor for Human Immunodeficiency Virus and Simian Immunodeficiency Viruses: A Prototypic Love-Hate Affair.Frontiers in immunology · 2022Review
- Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy.Frontiers in immunology · 2021Review
- Dopamine Levels Induced by Substance Abuse Alter Efficacy of Maraviroc and Expression of CCR5 Conformations on Myeloid Cells: Implications for NeuroHIV.Frontiers in immunology · 2021Article
- A biophysical perspective on receptor-mediated virus entry with a focus on HIV.Biochimica et biophysica acta. Biomembranes · 2020Review
- CCR5 structural plasticity shapes HIV-1 phenotypic properties.PLoS pathogens · 2018Article
- Evolution of Host Target Cell Specificity During HIV-1 Infection.Current HIV research · 2018Review
- Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Targeting of mTOR catalytic site inhibits multiple steps of the HIV-1 lifecycle and suppresses HIV-1 viremia in humanized mice.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Review
- Pros and cons of liver transplantation in human immunodeficiency virus infected recipients.World journal of gastroenterology · 2014Review
- Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.Retrovirology · 2014Article
- Coregulation of HIV-1 dependency factors in individuals heterozygous to the CCR5-delta32 deletion.AIDS research and therapy · 2013Article
- The microvesicle component of HIV-1 inocula modulates dendritic cell infection and maturation and enhances adhesion to and activation of T lymphocytes.PLoS pathogens · 2013Article
- Constitutively active CCR5 chemokine receptors differ in mediating HIV envelope-dependent fusion.PloS one · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently reported that the mean number of CCR5 coreceptors at the surface of CD4(+) T cells (CCR5 density) correlates with viral load and disease progression in HIV-1-infected persons. Here, we definitively establish that CCR5 density determines the level of virus production and identify the stages of HIV-1 replicative cycle modulated by this effect. We show, by transducing the CCR5 gene into CCR5(+) cells, that CCR5 overexpression resulted in an HIV-1 overinfectability. We sorted HOS-CD4(+)-CCR5(+) cells into two subpopulations, HOS(high) and HOS(low), the former expressing seven times more cell surface CCR5 molecules than the latter. Virus production was 30-80 times higher in HOS(high) cells than in HOS(low) cells after a single round of infection. In contrast, only twice as many viral particles entered the cytosol of HOS(high) cells as compared with the cytosol of HOS(low) cells. Yet, seven times as many early, and 24 times as many late, reverse transcription products were found in HOS(high) cells as compared with HOS(low) cells. Moreover, a 24- to 30-fold difference in the number of copies of integrated HIV-1 DNA was observed. No difference in HIV-1 LTR activation between the two cell lines was evident. Finally, we show that the higher virus production observed in HOS(high) cells is inhibited by pertussis toxin, a Galphai protein inhibitor. Thus, CCR5 density mainly modulates postentry steps of the virus life cycle, particularly the reverse transcription. These data explain why CCR5 density influences HIV-1 disease progression and underline the therapeutic interest of lowering CCR5 expression.
Indexed as
Identifiers
What OpenQuestion holds
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.