Affinage

CCR5

C-C chemokine receptor type 5 · UniProt P51681

Length
352 aa
Mass
40.5 kDa
Annotated
2026-06-09
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCR5 is a Gi-coupled seven-transmembrane chemokine receptor that binds the CC-chemokines MIP-1alpha (CCL3), MIP-1beta (CCL4), RANTES (CCL5), and MCP-2 (CCL8) as agonists and signals through pertussis-toxin-sensitive Gialpha2 to inhibit adenylyl cyclase and mobilize calcium (PMID:8699119, PMID:9736452, PMID:9468473). It serves as the principal coreceptor for macrophage-tropic (R5) HIV-1 entry, conferring envelope-mediated fusion and infection when co-expressed with CD4 in otherwise non-permissive cells, with which it forms a constitutive surface complex via its second extracellular loop and the first two CD4 domains (PMID:8649512, PMID:8658171, PMID:8674120, PMID:10377443). Agonist binding triggers GRK- and PKC-mediated C-terminal phosphorylation—including a pXpp phosphomotif at the receptor tail that is required for stable arrestin2 recruitment—driving desensitization and internalization through clathrin-coated pits and caveolae, with recycling routed through early endosomes and the trans-Golgi network under actin/Rho-GTPase control (PMID:9736452, PMID:11806977, PMID:12403770, PMID:14717692, PMID:37244255). Plasma-membrane delivery of CCR5 requires palmitoylation and TM5-mediated homodimerization, and the receptor adopts multiple conformational and oligomeric states that govern HIV-1 strain tropism and discriminate chemokine binding from allosteric small-molecule inhibitor binding, the structural basis exploited by maraviroc and aplaviroc (PMID:16476734, PMID:21775441, PMID:21878623, PMID:29739880, PMID:31663020). Beyond immune cell signaling, CCR5 drives hepatic stellate cell migration through a redox-sensitive PI3K pathway in fibrosis (PMID:19603542), and in the CNS controls neuronal excitability and the temporal window for memory linking (PMID:35614219) and suppresses neuronal autophagy via mTORC1 to impair clearance of aggregate-prone proteins (PMID:37105172).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established that CCR5 is the missing coreceptor enabling macrophage-tropic HIV-1 entry, answering why CD4 alone is insufficient for infection by these strains.

    Evidence Reconstitution of CCR5/CD4 in non-permissive human and non-human cells with infection and cell-cell fusion assays, across multiple HIV-1 strains

    PMID:8649512 PMID:8658171 PMID:8674120

    Open questions at the time
    • Did not resolve the gp120-CCR5 binding interface at atomic resolution
    • Did not establish the relative roles of CCR5 monomers vs oligomers in entry
  2. 1996 High

    Defined the native ligand and signaling identity of CCR5 as a Gi-coupled CC-chemokine receptor, distinguishing its physiological role from its HIV coreceptor function.

    Evidence Calcium flux and radioligand binding in transfected cells with pertussis toxin inhibition; CCL3/CCL4/CCL5 as agonists

    PMID:8699119

    Open questions at the time
    • Specific Galpha isoform coupling not yet pinned to Gialpha2
    • Downstream effector cascade beyond calcium/cAMP not defined
  3. 1998 High

    Showed CCR5 couples specifically to Gialpha2 to inhibit adenylyl cyclase and undergoes rapid agonist-dependent desensitization, defining its canonical GPCR output.

    Evidence GTPgammaS binding, adenylyl cyclase assay, Gialpha2 overexpression and pertussis toxin in stable CHO/NG108-15 cells; competitive binding and internalization for CCL8 as an additional agonist/HIV inhibitor

    PMID:9468473 PMID:9736452

    Open questions at the time
    • Quantitative contribution of each Galpha subtype in primary leukocytes unknown
    • Link between desensitization kinetics and HIV inhibition not fully resolved
  4. 1998 High

    Distinguished CCR5 endocytic machinery from CXCR4 by showing it is internalized by ligand but not phorbol esters, indicating a distinct C-terminal endocytosis signal.

    Evidence RANTES vs phorbol ester internalization assays and mutagenesis of endocytosis motifs

    PMID:9718374

    Open questions at the time
    • Precise residues governing constitutive vs ligand-induced uptake not mapped here
  5. 1999 Medium

    Demonstrated a pre-formed CD4-CCR5 complex on the cell surface, explaining the efficiency of the gp120-triggered entry mechanism.

    Evidence Reciprocal co-immunoprecipitation with domain mapping and functional antibody inhibition

    PMID:10377443

    Open questions at the time
    • Stoichiometry of the complex not determined
    • Single lab; structural model of the interface absent
  6. 2002 High

    Resolved the trafficking itinerary and phosphoregulation of CCR5, establishing how the receptor is internalized, phosphorylated, and recycled.

    Evidence Pharmacological pathway inhibitors with arrestin-2 tracking; phosphosite-specific antibodies identifying PKC at Ser337 and GRK at Ser349 with phosphatase dissection

    PMID:11806977 PMID:12403770

    Open questions at the time
    • Functional consequence of each phosphosite for signaling vs trafficking not fully separated
    • Identity of the responsible GRK isoform not established
  7. 2004 Medium

    Identified actin polymerization and Rho-family GTPases as cytoskeletal regulators of CCR5 internalization and recycling, linking receptor traffic to cell motility machinery.

    Evidence Cytochalasin D, Toxin B, C3 exoenzyme and Y27632 in CHO and THP-1 cells

    PMID:14717692

    Open questions at the time
    • Direct effectors connecting Rho GTPases to endocytic vesicles unidentified
    • Single lab, pharmacological inference
  8. 2006 High

    Localized small-molecule inhibitor and gp120 binding determinants to the TM cavity and extracellular loops, showing inhibitors can block HIV while sparing chemokine binding.

    Evidence Saturation binding and site-directed mutagenesis of CCR5 TM domains with gp120 binding and HIV infection assays; aplaviroc

    PMID:16476734

    Open questions at the time
    • Atomic-resolution structure of the inhibitor pocket not yet available
  9. 2008 Medium

    Revealed a CCR5-CXCR4 signaling complex required for chemokine-driven T-cell costimulation at the immunological synapse, extending CCR5 function into adaptive immune activation.

    Evidence Co-immunoprecipitation, live imaging of synapse recruitment, and costimulation assays in human T cells

    PMID:18632580

    Open questions at the time
    • Molecular interface of the CCR5-CXCR4 complex not mapped
    • Single lab
  10. 2009 High

    Extended CCR5 function to tissue fibrosis by showing it drives hepatic stellate cell migration through a redox/PI3K pathway.

    Evidence CCR5-deficient bone marrow chimeras with HSC migration assays, PI3K inhibitors, and fibrosis models

    PMID:19603542

    Open questions at the time
    • Downstream PI3K effectors in HSCs not specified
    • Relative contribution of resident vs infiltrating CCR5+ cells incompletely resolved
  11. 2011 Medium

    Defined the allosteric mechanism of maraviroc and the structural separation of orthosteric chemokine and allosteric inhibitor sites, clarifying how TM-cavity drugs antagonize an extracellular ligand.

    Evidence Mutagenesis with homology modeling/docking and CCR5/CCR2 chimeric receptor binding and signaling assays

    PMID:21775441 PMID:21878623

    Open questions at the time
    • Conclusions rely on homology to CXCR4 rather than CCR5 crystal structure
    • Allosteric communication pathway between sites not structurally defined
  12. 2018 High

    Established TM5-mediated homodimerization as a requirement for CCR5 plasma-membrane targeting and identified conformationally distinct receptor populations that shape HIV tropism.

    Evidence Cross-linking, FRET/BRET, RUSH export assay and TM5 mutagenesis; gp120 binding and entry assays across cell types with epitope mapping

    PMID:29739880 PMID:30521629

    Open questions at the time
    • Functional signaling differences between dimer states not fully resolved
    • In vivo relevance of conformational heterogeneity untested
  13. 2019 High

    Identified palmitoylation as a checkpoint for CCR5 secretory transport, providing a druggable node that limits surface expression and HIV entry.

    Evidence RUSH transport assay, high-content screening, palmitoylation assay, and HIV entry in primary macrophages

    PMID:31663020

    Open questions at the time
    • Responsible palmitoyl-acyltransferase not identified
    • Palmitoylation sites not individually mapped
  14. 2021 Medium

    Uncovered non-immune CCR5 signaling in disease: promotion of DNA-PKcs-mediated DNA repair and chemoresistance in glioblastoma, and PKA/CREB/NLRP1-dependent neuronal pyroptosis after hemorrhage.

    Evidence Pericyte depletion in GBM xenografts with maraviroc and DNA-PKcs assays; intranasal maraviroc and pathway inhibitors in an ICH mouse model

    PMID:34239070 PMID:34719258

    Open questions at the time
    • Mechanism linking CCR5 to DNA-PKcs activation not biochemically defined
    • Single lab per model; human relevance correlative
  15. 2022 High

    Defined a CNS role for CCR5 in regulating neuronal excitability and the temporal window for memory linking, with implications for age-related memory decline.

    Evidence CCR5 knockout and maraviroc with in vivo electrophysiology, neuronal ensemble labeling, and behavioral memory tests in mice

    PMID:35614219

    Open questions at the time
    • Signaling cascade from CCR5 to excitability changes not delineated
    • Source of neuronal CCL5 increase incompletely defined
  16. 2023 High

    Established that CCR5 suppresses neuronal autophagy via mTORC1 in a self-amplifying loop, linking microglial chemokine signaling to neurodegenerative proteostasis failure, and defined the structural basis of the CCR5-arrestin2 interaction.

    Evidence CCR5 knockout and pharmacology with mTORC1/autophagy assays in HD and tauopathy models; crystallography, NMR and mutagenesis of the pXpp arrestin2 phosphomotif

    PMID:37105172 PMID:37244255

    Open questions at the time
    • G-protein vs arrestin bias in neuronal autophagy signaling not dissected
    • Full-length CCR5-arrestin2 complex structure not solved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCR5 conformational and oligomeric heterogeneity, biased signaling, and tissue-specific effector coupling are integrated into a single regulatory logic across immune, neural, fibrotic and oncogenic contexts remains unresolved.
  • No unified model linking dimer state to ligand-, G-protein-, and arrestin-biased outputs
  • Tissue-specific determinants of CCR5 effector choice unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Partners
ARRB2CCL3CCL4CCL5CCL8CD4CXCR4GNAI2
Complex memberships
CCR5 homodimerCCR5-CXCR4 heterodimer/signaling complexCD4-CCR5 entry complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 CC-CKR-5 (CCR5) functions as a second receptor (coreceptor) for NSI/macrophage-tropic HIV-1 strains: expression of CCR5 in CD4+, non-permissive human and non-human cells renders them susceptible to infection by NSI strains and allows env-mediated membrane fusion. Expression of CCR5 in non-permissive CD4+ cells, infection assay and cell-cell fusion assay Nature High 8649512 8658171 8674120
1996 CC CKR5 is a G protein-coupled receptor for RANTES, MIP-1alpha, and MIP-1beta, and serves as a fusion cofactor specifically for macrophage-tropic (R5) HIV-1 envelope glycoproteins; CCR5 mRNA expression is selective for cell types susceptible to macrophage-tropic isolates. Recombinant CCR5 expression in CD4+ non-human cells, cell fusion assay with macrophage-tropic vs. T-cell line-tropic Envs, RT-PCR for CCR5 mRNA in susceptible cell types Science High 8658171
1996 CKR-5 (CCR5) functions as a cofactor for M-tropic HIV-1 entry and cell-cell syncytia formation when co-expressed with CD4; a dual-tropic HIV-1 isolate (89.6) can use both CCR5 and Fusin (CXCR4) as entry cofactors. Expression of CCR5/CD4 in non-permissive QT6 cells, syncytia formation and viral entry assays Cell High 8674120
1996 CCR5 selectively binds MIP-1alpha, MIP-1beta, and RANTES as agonists (EC50 = 3–30 nM for calcium flux); CCR5-mediated calcium flux responses are completely blocked by pertussis toxin, indicating coupling to Gi-class G proteins. Calcium flux assay in transfected HEK 293 cells, pertussis toxin inhibition, radioligand binding assay Journal of leukocyte biology High 8699119
1998 CCR5 activation by RANTES stimulates membrane-associated inhibitory G proteins (specifically Gialpha2), inhibits adenylyl cyclase activity (reducing cAMP), and undergoes rapid agonist-dependent desensitization and internalization; these effects are blocked by pertussis toxin. [35S]GTPgammaS binding assay, adenylyl cyclase inhibition assay, Gialpha2 overexpression, pertussis toxin treatment, flow cytometry for surface receptor levels in stably transfected CHO and NG108-15 cells Journal of cellular biochemistry High 9736452
1998 MCP-2 (CCL8) binds and activates CCR5 (competing with MIP-1beta binding), induces CCR5 internalization, and blocks HIV-1 entry/replication in CCR5/CD4-co-expressing cells, identifying MCP-2 as an additional natural CCR5 agonist and HIV-1 inhibitor. Competitive radioligand binding on CCR5-transfected HEK293 cells, chemotaxis assay, confocal microscopy for receptor internalization, HIV-1 infection assay The Journal of biological chemistry High 9468473
1998 CCR5 internalization is induced by the beta-chemokine RANTES but not by phorbol esters; CCR5 lacks the Ser/IleLeu sequence required for phorbol ester-induced uptake seen with CXCR4, indicating distinct endocytosis mechanisms for CCR5 vs. CXCR4. Internalization assays with RANTES and phorbol esters, mutagenesis of endocytosis signal motifs, comparison with CXCR4 Journal of cell science High 9718374
1999 CD4 and CCR5 are constitutively associated on the cell surface in the absence of gp120; this interaction involves the second extracellular loop of CCR5 and the first two domains of CD4, and can be inhibited by CCR5- and CD4-specific antibodies that also interfere with HIV-1 infection. Co-immunoprecipitation, antibody competition assay, comparison with CD4-CXCR4 co-IP Proceedings of the National Academy of Sciences of the United States of America Medium 10377443
2002 CCR5 undergoes ligand-induced internalization via clathrin-coated pits (inhibited by sucrose, associated with arrestin-2 translocation) and caveolae (inhibited by nystatin/filipin); CCR5 recycling to the cell surface is independent of the Golgi apparatus and late endosomes, consistent with routing through early endosomes. Pharmacological inhibitors (sucrose, nystatin, filipin, vesicle transport inhibitors), arrestin-2 movement tracking, receptor recovery assays in CCR5-expressing CHO cells Blood Medium 11806977
2002 Following CCR5 ligand stimulation, serine 337 is phosphorylated exclusively by PKC in a rapid but transient manner, while serine 349 is phosphorylated by GRK in a time-dependent manner; phosphorylated receptors accumulate in perinuclear recycling endosomes; protein phosphatases active at neutral pH dephosphorylate these sites. Phosphosite-specific monoclonal antibodies, immunofluorescence microscopy, in vitro phosphatase assay with okadaic acid in CCR5-expressing cells The Journal of biological chemistry High 12403770
2004 CCR5 internalization and recycling are regulated by actin polymerization and activation of small GTPases (Rho family); treatment with cytochalasin D (actin depolymerizer), Toxin B, or C3 exoenzyme inhibited both CCR5 internalization and recycling; Rho kinase inhibitor Y27632 had no effect on internalization/recycling but ligand-induced CCR5 activation leads to Rho kinase-dependent focal adhesion complex formation. Pharmacological inhibitors (cytochalasin D, Toxin B, C3 exoenzyme, Y27632), stably transfected CHO cells and monocytic THP-1 cells European journal of biochemistry Medium 14717692
2006 CCR5 inhibitors (including aplaviroc) bind in a predominantly lipophilic pocket at the interface of extracellular loops and within the upper transmembrane (TM) domain of CCR5; mutations in CCR5 binding sites decreased both gp120 binding to CCR5 and HIV-1 susceptibility; mutations in TM4/TM5 decreased gp120 binding and HIV-1 infectivity with less effect on CC-chemokine binding, indicating that appropriate CCR5 inhibitor binding can be HIV-1-specific while preserving chemokine-CCR5 interactions. Saturation binding assays, site-directed mutagenesis of CCR5 TM domains, gp120 binding assay, HIV-1 infection assay The Journal of biological chemistry High 16476734
2008 CCR5 and CXCR4 physically associate in a signaling complex; simultaneous expression and cooperation between CCR5 and CXCR4 are required for chemokine-induced T cell costimulation at the immunological synapse; CCR5 is recruited to the immunological synapse during human T cell activation. Co-immunoprecipitation demonstrating physical association, live imaging of receptor recruitment to the immunological synapse, functional costimulation assays in human T cells Proceedings of the National Academy of Sciences of the United States of America Medium 18632580
2009 CCR5 mediates its profibrogenic effects in resident liver cells (hepatic stellate cells, HSCs), promoting HSC migration through a redox-sensitive, PI3K-dependent pathway; CCR5-deficient HSCs display strongly suppressed CC chemokine-induced migration. CCR5-deficient mouse chimeras (bone marrow transplant), in vitro HSC migration assays with PI3K inhibitors and redox manipulation, experimental fibrosis models The Journal of clinical investigation High 19603542
2010 During CCR5 desensitization, the receptor cycles to and from the cell surface via the endosome recycling compartment and the trans-Golgi network; both the native ligand CCL5 and the chemokine analog PSC-RANTES cause CCR5 accumulation in the trans-Golgi network, but CCR5 sequestered by PSC-RANTES cannot be returned to the cell surface by the small molecule inhibitor TAK-779 and shows more durable association with CCR5 than CCL5. Fluorescence microscopy, subcellular fractionation, inhibitor competition assays in CCR5-expressing cells The Journal of biological chemistry Medium 21041313
2011 Maraviroc binds CCR5 at a transmembrane cavity and prevents CCL3 and gp120 binding by an allosteric mechanism; maraviroc can insert in three different binding positions in the TM cavity; residues in the CCR5 dimer interface are required for gp120 binding, suggesting receptor dimerization is important for HIV-1 entry. Site-directed mutagenesis combined with homology modeling, automated docking using CXCR4 crystal structure, virtual screening, CCR5 chimera analysis The Journal of biological chemistry Medium 21775441
2011 Using CCR5/CCR2 chimeric receptors, orthosteric chemokine binding sites (extracellular) and allosteric small molecule binding sites (transmembrane) in CCR5 can be structurally separated yet still functionally communicate agonism and antagonism; allosteric enhancement of chemokine binding is disrupted when extracellular regions are replaced. CCR5/CCR2 chimeric receptor construction, ligand binding assays, signaling assays, CCR5-selective small molecule agonist/antagonist testing The Journal of biological chemistry Medium 21878623
2018 CCR5 forms three distinct homodimeric conformations involving transmembrane helix 5; two dimeric states correspond to unliganded receptors and one is stabilized by the inverse agonist maraviroc; CCR5 dimerization is required for targeting the receptor to the plasma membrane. Receptor cross-linking, FRET/BRET energy transfer, functional export assay (RUSH system), computational modeling, site-directed mutagenesis of TM5 interface residues Science signaling High 29739880
2018 CCR5 exists in multiple structurally and antigenically distinct conformations at the cell surface; gp120s from different HIV-1 strains exhibit divergent binding to different CCR5 populations/conformations; HIV-1 preferentially uses CCR5 monomers (not oligomers) for entry; CCR5 conformational diversity shapes HIV-1 cellular tropism and sensitivity to CCR5 ligand inhibition. Mutagenesis of CCR5 dimerization interface, gp120 binding assays on cell lines and primary cells, viral entry assays, CD4i monoclonal antibody epitope mapping, T-cell vs. macrophage CCR5 comparison PLoS pathogens Medium 30521629
2019 CCR5 palmitoylation is critical for its delivery to the plasma membrane via the secretory pathway; small molecules that inhibit CCR5 palmitoylation trap CCR5 in the early secretory pathway, reducing plasma membrane expression and markedly decreasing HIV entry in primary macrophages. Cell-based assay monitoring differential protein transport (RUSH), high-content screening, palmitoylation assay, HIV entry assay in primary macrophages Science advances High 31663020
2021 CCR5 activation by CCL5 (from pericytes) promotes DNA-PKcs-mediated DNA damage repair in glioblastoma cells, inducing temozolomide chemoresistance; disrupting CCL5-CCR5 paracrine signaling with maraviroc inhibits pericyte-promoted DDR. Genetic depletion of pericytes in GBM xenografts, CCR5 activation/inhibition (maraviroc), DNA-PKcs assay, survival analysis in tumor-bearing mice, patient-derived xenografts Cell research Medium 34239070
2021 CCR5 activation in neurons after intracerebral hemorrhage promotes neuronal pyroptosis via the CCR5/PKA/CREB/NLRP1 signaling pathway: CCR5 activation suppresses PKA-Cα and p-CREB, which upregulates NLRP1/ASC/caspase-1/GSDMD and IL-1β/IL-18; CCR5 inhibition with maraviroc or PKA activation reversed these effects. Intranasal maraviroc administration in ICH mice, CREB inhibitor (666-15) intracerebroventricular injection, rCCL5 and 8-Bromo-cAMP intracerebroventricular injection, Western blot, immunofluorescence, behavioral assays Stroke Medium 34719258
2022 A delayed (12–24 h) increase in CCR5 expression in mouse dorsal CA1 neurons after contextual memory formation decreases neuronal excitability, reduces overlap between memory ensembles, and closes the temporal window for memory linking; age-related increase in neuronal CCR5 and CCL5 impairs memory linking, reversible by CCR5 knockout or maraviroc. CCR5 knockout mice, maraviroc pharmacological inhibition, in vivo electrophysiology (neuronal excitability), activity-dependent neuronal labeling (memory ensemble overlap), behavioral memory linking tests in mice Nature High 35614219
2023 Activated microglial-derived CCL3/CCL4/CCL5 bind neuronal CCR5 and activate mTORC1, inhibiting neuronal autophagy and impairing clearance of aggregate-prone proteins; CCR5 upregulation is self-sustaining because CCL5-CCR5-mediated autophagy inhibition impairs CCR5 degradation itself; pharmacological or genetic CCR5 inhibition rescues autophagy and ameliorates Huntington's disease and tau pathology in mice. CCR5 knockout mice, pharmacological CCR5 inhibition, mTORC1 activity assays, autophagy flux assays, aggregate-prone protein clearance assays, HD and tauopathy mouse models Neuron High 37105172
2023 CCR5 C-terminal phosphorylation at a pXpp motif (three phosphoresidues) is essential for stable arrestin2 complex formation; crystal structures of arrestin2 with CCR5 C-terminal phosphopeptides revealed the structural basis of this interaction; GRK- and PKC-mediated multi-site phosphorylation controls the CCR5-arrestin2 interaction. X-ray crystallography of arrestin2-CCR5 phosphopeptide complexes, NMR, site-directed mutagenesis of CCR5 phosphorylation sites, biochemical pulldown assays, functional arrestin recruitment assays Molecular cell High 37244255
2023 CCR5 and CXCR4 form symmetric and asymmetric homodimers and heterodimers; CCR5/CCR5 homodimers preferentially use TM4-TM5 as the binding interface; CXCR4/CXCR4 uses TM6-TM7; distinct dimeric states differ in access to ligand and G protein binding sites, suggesting dimerization as an allosteric regulatory mechanism. Coarse-grained metadynamics free-energy simulation (computational), validated against existing structural and functional data Nature communications Low 37833254
2018 CCR5 downregulation by RANKL is mediated through MEK and JNK signaling pathways in preosteoclast cells; CCR5 downregulation promotes osteoclastogenesis; IFN-γ can restore RANKL-reduced CCR5 expression. MEK and JNK inhibitors, Western blot, osteoclast differentiation assay, migration assay in mouse preosteoclast cells Cell death & disease Medium 29717113
2012 CCL5-CCR5 interaction in osteosarcoma cells activates MEK, ERK, and NF-κB pathways, resulting in upregulation of αvβ3 integrin and enhanced cell migration; CCR5 siRNA/mAb/inhibitor reduced CCL5-enhanced migration and integrin upregulation. CCR5 siRNA knockdown, CCR5 mAb blocking, kinase pathway inhibitors (MEK, ERK, NF-κB dominant-negative mutants), migration assay, integrin expression by flow cytometry PloS one Medium 22506069
2020 IL-6 upregulates CCR5 expression and arginase 1 in MDSCs through a STAT3-dependent mechanism; CCR5+ MDSCs differentiated in the presence of IL-6 exhibit strongly enhanced immunosuppressive activity. In vitro MDSC differentiation with IL-6, STAT3 inhibition, RT-PCR and Western blot for CCR5/arginase 1, T cell suppression assay, validation in RET transgenic melanoma mouse model Journal for immunotherapy of cancer Medium 32788238

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 2758 8649512
1996 CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science (New York, N.Y.) 2372 8658171
1996 A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 1669 8674120
2009 CCR1 and CCR5 promote hepatic fibrosis in mice. The Journal of clinical investigation 372 19603542
2001 Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice. Journal of immunology (Baltimore, Md. : 1950) 369 11254730
2020 The CCL5/CCR5 Axis in Cancer Progression. Cancers 313 32630699
2004 Chemokine receptor CCR5: insights into structure, function, and regulation. Cellular signalling 297 15337520
1996 Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RANTES. Journal of leukocyte biology 245 8699119
2006 Biology of CCR5 and its role in HIV infection and treatment. JAMA 205 16905787
2006 Expression of CCL5 (RANTES) and CCR5 in prostate cancer. The Prostate 197 16161154
1997 Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals. AIDS (London, England) 193 9147421
2019 Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology. Cancer research 192 31292161
2008 CXCR4-CCR5: a couple modulating T cell functions. Proceedings of the National Academy of Sciences of the United States of America 191 18632580
2009 The biology of CCR5 and CXCR4. Current opinion in HIV and AIDS 163 19339947
2011 Chemokine receptor CCR5: from AIDS to atherosclerosis. British journal of pharmacology 161 21133894
1999 Constitutive cell surface association between CD4 and CCR5. Proceedings of the National Academy of Sciences of the United States of America 160 10377443
2017 CCR5+ Myeloid-Derived Suppressor Cells Are Enriched and Activated in Melanoma Lesions. Cancer research 154 29089297
1997 Macrophage tropism of human immunodeficiency virus type 1 and utilization of the CC-CKR5 coreceptor. Journal of virology 146 8995695
2005 The case for selection at CCR5-Delta32. PLoS biology 142 16248677
2021 Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling. Cell research 134 34239070
2006 Structural and molecular interactions of CCR5 inhibitors with CCR5. The Journal of biological chemistry 132 16476734
2002 Pathways for internalization and recycling of the chemokine receptor CCR5. Blood 127 11806977
1997 Novel alleles of the chemokine-receptor gene CCR5. American journal of human genetics 127 9399903
1998 Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication. The Journal of biological chemistry 121 9468473
2016 CCR5 blockade for neuroinflammatory diseases--beyond control of HIV. Nature reviews. Neurology 117 26782333
1998 Differential regulation of CXCR4 and CCR5 endocytosis. Journal of cell science 117 9718374
2003 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways. Journal of leukocyte biology 110 12960231
2020 IL-6 regulates CCR5 expression and immunosuppressive capacity of MDSC in murine melanoma. Journal for immunotherapy of cancer 108 32788238
2021 CCR5 Activation Promotes NLRP1-Dependent Neuronal Pyroptosis via CCR5/PKA/CREB Pathway After Intracerebral Hemorrhage. Stroke 107 34719258
1997 Expression of the human immunodeficiency virus type-1 coreceptors CXCR-4 (fusin, LESTR) and CKR-5 in CD34+ hematopoietic progenitor cells. Blood 107 9160656
2011 Allosteric model of maraviroc binding to CC chemokine receptor 5 (CCR5). The Journal of biological chemistry 104 21775441
2005 The evolutionary history of the CCR5-Delta32 HIV-resistance mutation. Microbes and infection 98 15715976
2023 Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration. Neuron 95 37105172
2014 The potential to target CCL5/CCR5 in breast cancer. Expert opinion on therapeutic targets 94 25256399
2010 Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases. Journal of leukocyte biology 92 20360402
2004 The chemokine receptor, CCR5. The international journal of biochemistry & cell biology 89 14592532
2012 CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma. PloS one 88 22506069
2018 The Expanding Therapeutic Perspective of CCR5 Blockade. Frontiers in immunology 85 29375583
2010 The chemokine receptor CCR5 in the central nervous system. Progress in neurobiology 82 21163326
2022 CCR5 closes the temporal window for memory linking. Nature 81 35614219
2019 CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome. Nature immunology 81 31209403
1996 The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1-CMKBR5) are clustered in the p21.3-p24 region of chromosome 3. Genomics 81 8884276
2011 Clinical use of CCR5 inhibitors in HIV and beyond. Journal of translational medicine 80 21284908
2018 CCR5 antagonism by maraviroc inhibits Hodgkin lymphoma microenvironment interactions and xenograft growth. Haematologica 75 30309853
2006 T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery. Gene therapy 74 16738691
2018 CCR5 Revisited: How Mechanisms of HIV Entry Govern AIDS Pathogenesis. Journal of molecular biology 72 29932942
2013 Relationship between the chemokine receptor CCR5 and microglia in neurological disorders: consequences of targeting CCR5 on neuroinflammation, neuronal death and regeneration in a model of epilepsy. CNS & neurological disorders drug targets 70 24047524
2002 CCR5 and HIV infection. Receptors & channels 68 12402506
2015 CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape. Viruses 66 26225991
2019 Cytokine CCL5 and receptor CCR5 axis in glioblastoma multiforme. Radiology and oncology 63 31747383
2004 Evolutionary genetics: CCR5 mutation and plague protection. Nature 62 14961112
2005 CCR5 expression and CC chemokine levels in idiopathic pulmonary fibrosis. The European respiratory journal 60 15802346
2010 CC chemokine receptor 5 (CCR5) desensitization: cycling receptors accumulate in the trans-Golgi network. The Journal of biological chemistry 58 21041313
2002 Analysis of ligand-stimulated CC chemokine receptor 5 (CCR5) phosphorylation in intact cells using phosphosite-specific antibodies. The Journal of biological chemistry 55 12403770
2009 Maraviroc: a new CCR5 antagonist. Expert review of anti-infective therapy 54 19622053
1998 Chemokine receptor CCR5 functionally couples to inhibitory G proteins and undergoes desensitization. Journal of cellular biochemistry 54 9736452
2007 CCR5 receptor: biologic and genetic implications in age-related diseases. Annals of the New York Academy of Sciences 51 17460174
2016 Role of interleukin-4, the chemokine CCL3 and its receptor CCR5 in neuropathic pain. Molecular immunology 50 27522478
2007 CCR5 blockade modulates inflammation and alloimmunity in primates. Journal of immunology (Baltimore, Md. : 1950) 50 17675490
2021 CCR5 is a potential therapeutic target for cancer. Expert opinion on therapeutic targets 49 33719836
2019 The human tissue-resident CCR5+ T cell compartment maintains protective and functional properties during inflammation. Science translational medicine 49 31801887
2004 Hypoxia inhibits the expression of the CCR5 chemokine receptor in macrophages. Cellular immunology 46 15203313
2020 Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases. Virus research 43 32479976
2011 Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach. The Journal of biological chemistry 42 21878623
2019 CCR5 status and metastatic progression in colorectal cancer. Oncoimmunology 41 31428524
2017 Relevance of CCL3/CCR5 axis in oral carcinogenesis. Oncotarget 41 28881626
2020 Advances of CCR5 antagonists: From small molecules to macromolecules. European journal of medicinal chemistry 40 32947226
2018 CCR5 adopts three homodimeric conformations that control cell surface delivery. Science signaling 40 29739880
1998 Cloning of rat HIV-1-chemokine coreceptor CKR5 from microglia and upregulation of its mRNA in ischemic and endotoxinemic rat brain. Journal of neuroscience research 40 9670989
2018 CCL4 enhances preosteoclast migration and its receptor CCR5 downregulation by RANKL promotes osteoclastogenesis. Cell death & disease 39 29717113
2012 CCR5 inhibitors: emergence, success, and challenges. Expert opinion on emerging drugs 38 22533737
1999 Chemokine-induced phosphorylation of CC chemokine receptor 5 (CCR5). Journal of leukocyte biology 38 10080528
2004 Expression of DARC, CXCR3 and CCR5 in giant cell arteritis. Rheumatology (Oxford, England) 37 15572394
2023 TGFβ1+CCR5+ neutrophil subset increases in bone marrow and causes age-related osteoporosis in male mice. Nature communications 36 36631487
2015 Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion. Acta biochimica et biophysica Sinica 36 26390883
2023 Structural basis of dimerization of chemokine receptors CCR5 and CXCR4. Nature communications 34 37833254
2005 Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA). Antiviral research 34 16002156
2004 Mechanisms of internalization and recycling of the chemokine receptor, CCR5. European journal of biochemistry 34 14717692
2023 A key GPCR phosphorylation motif discovered in arrestin2⋅CCR5 phosphopeptide complexes. Molecular cell 32 37244255
2021 Dual role for CXCR3 and CCR5 in asthmatic type 1 inflammation. The Journal of allergy and clinical immunology 32 34146578
2017 Knockdown of C-C Chemokine Receptor 5 (CCR5) is Protective Against Cerebral Ischemia and Reperfusion Injury. Current neurovascular research 31 28294064
2017 CCR5-edited gene therapies for HIV cure: Closing the door to viral entry. Cytotherapy 31 28751153
2014 Targeting spare CC chemokine receptor 5 (CCR5) as a principle to inhibit HIV-1 entry. The Journal of biological chemistry 29 24855645
2013 CCR5 as a natural and modulated target for inhibition of HIV. Viruses 29 24381033
2009 CCR5 monoclonal antibodies for HIV-1 therapy. Current opinion in HIV and AIDS 29 19339948
2006 The Black Death and AIDS: CCR5-Delta32 in genetics and history. QJM : monthly journal of the Association of Physicians 29 16880184
2004 CC-chemokine receptor 5 (CCR5) in hepatitis C--at the crossroads of the antiviral immune response? The Journal of antimicrobial chemotherapy 29 15128728
2018 CCR5 structural plasticity shapes HIV-1 phenotypic properties. PLoS pathogens 28 30521629
2024 CCR5 and inflammatory storm. Ageing research reviews 27 38561044
2023 A novel small-molecular CCR5 antagonist promotes neural repair after stroke. Acta pharmacologica Sinica 27 37198412
2018 The return of PRO 140, a CCR5-directed mAb. Current opinion in HIV and AIDS 25 29708899
2018 CCR5: Established paradigms and new frontiers for a 'celebrity' chemokine receptor. Cytokine 25 29903576
2011 CCR5 mediates pro-osteoclastic and osteoclastogenic leukocyte chemoattraction. Journal of dental research 25 21245464
2024 Blockade of CCR5+ T Cell Accumulation in the Tumor Microenvironment Optimizes Anti-TGF-β/PD-L1 Bispecific Antibody. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 24 39303165
2019 Targeting CCR5 trafficking to inhibit HIV-1 infection. Science advances 24 31663020
2015 Editing CCR5: a novel approach to HIV gene therapy. Advances in experimental medicine and biology 24 25757618
2013 CCR2 and CCR5 genes polymorphisms in benign prostatic hyperplasia and prostate cancer. Human immunology 24 23632061
2022 CCR4 and CCR5 Involvement in Monocyte-Derived Macrophage Migration in Neuroinflammation. Frontiers in immunology 23 35634277
2019 CCR5-Positive Inflammatory Monocytes are Crucial for Control of Sepsis. Shock (Augusta, Ga.) 23 30724784
2019 Entanglement of CCR5 and Alzheimer's Disease. Frontiers in aging neuroscience 22 31447666

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