ArticleProceedings of the National Academy of Sciences of the United States of America2003
Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV beta-chemokines: an approach to suppress R5 strains of HIV-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Association of the CCR5 gene with juvenile idiopathic arthritis.Genes and immunity · 2010Pooled it
- Coadministration of rapamycin with a DNA/MVA SIV vaccine improves memory CD8+ T cell response.JCI insight · 2026Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.Cell reports. Medicine · 2024Article
- Bafilomycin A1 Inhibits HIV-1 Infection by Disrupting Lysosomal Cholesterol Transport.Viruses · 2024Article
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- CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Molecular and therapeutic insights of rapamycin: a multi-faceted drug from Streptomyces hygroscopicus.Molecular biology reports · 2023Review
- The Many Faces of Immune Activation in HIV-1 Infection: A Multifactorial Interconnection.Biomedicines · 2023Review
- mTOR regulation of metabolism limits LPS-induced monocyte inflammatory and procoagulant responses.Communications biology · 2022Article
- Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.The Journal of clinical investigation · 2022Article
- Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo.Scientific reports · 2022Article
- Cure and Long-Term Remission Strategies.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Review
- Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Immunometabolism and HIV-1 pathogenesis: food for thought.Nature reviews. Immunology · 2021Review
- HIV-Related Immune Activation and Inflammation: Current Understanding and Strategies.Journal of immunology research · 2021 · on this mapReview
- Block-And-Lock: New Horizons for a Cure for HIV-1.Viruses · 2020Review
- Organ transplantation in persons with HIV.AIDS (London, England) · 2020Review
- Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Propagation of R5 strains of HIV-1 on CD4 lymphocytes and macrophages requires expression of the CCR5 coreceptor on the cell surface. Individuals lacking CCR5 (CCR5 Delta 32 homozygous genotype) are phenotypically normal and resistant to infection with HIV-1. CCR5 expression on lymphocytes depends on signaling through the IL-2 receptor. By FACS analysis we demonstrate that rapamycin (RAPA), a drug that disrupts IL-2 receptor signaling, reduces CCR5 surface expression on T cells at concentrations as low as 1 nM. In addition, lower concentrations of RAPA (0.01 nM) were sufficient to reduce CCR5 surface expression on maturing monocytes. PCR analysis on peripheral blood mononuclear cells (PBMCs) showed that RAPA interfered with CCR5 expression at the transcriptional level. Reduced expression of CCR5 on PBMCs cultured in the presence of RAPA was associated with increased extracellular levels of macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. In infectivity assays, RAPA suppressed the replication of R5 strains of HIV-1 both in PBMC and macrophage cultures. In total PBMC cultures, RAPA-mediated inhibition of CCR5-using strains of HIV-1 occurred at 0.01 nM, a concentration of drug that is approximately 103 times lower than therapeutic through levels of drug in renal transplant recipients. In addition, RAPA enhanced the antiviral activity of the CCR5 antagonist TAK-779. These results suggest that low concentrations of RAPA may have a role in both the treatment and prevention of HIV-1 infection.
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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.