Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection.

The chemokine receptor CCR5 has recently been described as a co-receptor for macrophage-tropic strains of human immunodeficiency virus (HIV)-1. In this study, using a panel of monoclonal antibodies specific for human CCR5, we show by immunohistochemistry and flow cytometry that CCR5 is expressed by bone-marrow-derived cells known to be targets for HIV-1 infection, including a subpopulation of lymphocytes and monocyte/macrophages in blood, primary and secondary lymphoid organs, and noninflamed tissues. In the central nervous system, CCR5 is expressed on neurons, astrocytes, and microglia. In other tissues, CCR5 is expressed on epithelium, endothelium, vascular smooth muscle, and fibroblasts. Chronically inflamed tissues contain an increased number of CCR5+ mononuclear cells, and the number of immunoreactive cells is directly associated with a histopathological correlate of inflammatory severity. Collectively, these results suggest that CCR5+ cells are recruited to inflammatory sites and, as such, may facilitate transmission of macrophage-tropic strains of HIV-1.

[1]  J. Sodroski,et al.  CCR5 Levels and Expression Pattern Correlate with Infectability by Macrophage-tropic HIV-1, In Vitro , 1997, The Journal of experimental medicine.

[2]  C. Broder,et al.  Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D. Ho,et al.  Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry , 1997, Journal of virology.

[4]  L. Schweitzer,et al.  Expression of chemokine receptors by subsets of neurons in the central nervous system. , 1997, Journal of immunology.

[5]  J. Sodroski,et al.  Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239 , 1997, Journal of virology.

[6]  Richard A Koup,et al.  Homozygous Defect in HIV-1 Coreceptor Accounts for Resistance of Some Multiply-Exposed Individuals to HIV-1 Infection , 1996, Cell.

[7]  Ying Sun,et al.  The β-Chemokine Receptors CCR3 and CCR5 Facilitate Infection by Primary HIV-1 Isolates , 1996, Cell.

[8]  C. Broder,et al.  CC CKR5: A RANTES, MIP-1α, MIP-1ॆ Receptor as a Fusion Cofactor for Macrophage-Tropic HIV-1 , 1996, Science.

[9]  Virginia Litwin,et al.  HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5 , 1996, Nature.

[10]  Stephen C. Peiper,et al.  Identification of a major co-receptor for primary isolates of HIV-1 , 1996, Nature.

[11]  J. Glass,et al.  Localization of HIV‐1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry , 1996, Annals of neurology.

[12]  Paul E. Kennedy,et al.  HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor , 1996, Science.

[13]  S. Crowe,et al.  The interaction of macrophage and non-macrophage tropic isolates of HIV- 1 with thymic and tonsillar dendritic cells in vitro , 1996, The Journal of experimental medicine.

[14]  K. Chung,et al.  Expression of RANTES in human airway epithelial cells: effect of corticosteroids and interleukin‐4, ‐10 and ‐13 , 1996, Immunology.

[15]  G Vassart,et al.  Molecular cloning and functional expression of a new human CC-chemokine receptor gene. , 1996, Biochemistry.

[16]  A. Perelson,et al.  HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time , 1996, Science.

[17]  J. Warren,et al.  Inhibition of T cell recruitment and cutaneous delayed-type hypersensitivity-induced inflammation with antibodies to monocyte chemoattractant protein-1. , 1996, The American journal of pathology.

[18]  W Newman,et al.  Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. , 1996, The Journal of clinical investigation.

[19]  Zhaohua Lu,et al.  The Duffy antigen receptor for chemokines: structural analysis and expression in the brain , 1996, Journal of leukocyte biology.

[20]  S. Arya,et al.  Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells , 1995, Science.

[21]  G. Mariani,et al.  Productive HIV‐1 infection of human vascular endothelial cells requires cell proliferation and is stimulated by combined treatment with interleukin‐1β plus tumor necrosis factor‐α , 1995, Journal of medical virology.

[22]  T. Kupper,et al.  Acutely infected Langerhans cells are more efficient than T cells in disseminating HIV type 1 to activated T cells following a short cell-cell contact. , 1995, AIDS research and human retroviruses.

[23]  Dermot Maher,et al.  Prevalence of genital infections in medical inpatients in Blantyre, Malawi. , 1995, Journal of Infection.

[24]  H. Kleinman,et al.  Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo , 1995, The Journal of experimental medicine.

[25]  R. Hogg,et al.  Rectal gonorrhoea as an independent risk factor for HIV infection in a cohort of homosexual men. , 1995, Genitourinary medicine.

[26]  G. Randolph,et al.  Chemokines and tissue injury. , 1995, The American journal of pathology.

[27]  A. Waage,et al.  Antigen presentation by human fetal astrocytes with the cooperative effect of microglia or the microglial-derived cytokine IL-1 , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  A. Perelson,et al.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection , 1995, Nature.

[29]  T. Schall,et al.  Chemokines, leukocyte trafficking, and inflammation. , 1994, Current opinion in immunology.

[30]  R. Horuk Molecular properties of the chemokine receptor family. , 1994, Trends in pharmacological sciences.

[31]  D. Montefiori,et al.  Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques , 1994, Journal of virology.

[32]  T. Springer Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm , 1994, Cell.

[33]  D. Ho,et al.  Genotypic and phenotypic characterization of HIV-1 patients with primary infection. , 1993, Science.

[34]  R. Strieter,et al.  Interleukin-8 as a macrophage-derived mediator of angiogenesis. , 1992, Science.

[35]  J. Goudsmit,et al.  Epitopes of human immunodeficiency virus regulatory proteins tat, nef, and rev are expressed in normal human tissue. , 1992, The American journal of pathology.

[36]  Erwin G. Van Meir,et al.  Interleukin-8 is produced in neoplastic and infectious diseases of the human central nervous system. , 1992, Cancer research.

[37]  C. Fox,et al.  Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA. , 1991, The Journal of infectious diseases.

[38]  D. Silberberg,et al.  Galactosyl ceramide or a derivative is an essential component of the neural receptor for human immunodeficiency virus type 1 envelope glycoprotein gp120. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[39]  B. Chesebro,et al.  Failure of human immunodeficiency virus entry and infection in CD4-positive human brain and skin cells , 1990, Journal of virology.

[40]  C. Wiley,et al.  HUMAN IMMUNODEFICIENCY VIRUS DETECTED IN BOWEL EPITHELIUM FROM PATIENTS WITH GASTROINTESTINAL SYMPTOMS , 1988, The Lancet.

[41]  N. Brousse,et al.  AIDS subacute encephalitis. Identification of HIV-infected cells. , 1987, The American journal of pathology.

[42]  H. Gendelman,et al.  Productive, persistent infection of human colorectal cell lines with human immunodeficiency virus , 1987, Journal of virology.

[43]  H. Gendelman,et al.  Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. , 1986, Science.

[44]  D. Markovitz,et al.  The role of mononuclear phagocytes in HTLV-III/LAV infection. , 1986, Science.

[45]  M. Dietrich,et al.  ALTERED FOLLICULAR DENDRITIC CELLS AND VIRUS-LIKE PARTICLES IN AIDS AND AIDS-RELATED LYMPHADENOPATHY , 1985, The Lancet.

[46]  A. Moses,et al.  HIV infection of human brain capillary endothelial cells--implications for AIDS dementia. , 1994, Advances in neuroimmunology.

[47]  H. Koren,et al.  Constitutive and stimulated MCP-1, GROα, β, and γ expression in human airway epithelium and bronchoalveolar macrophages , 1994 .

[48]  M. Laga,et al.  Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. , 1993, AIDS.

[49]  H. Stein,et al.  Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells. , 1992, The American journal of pathology.

[50]  D. Dickson,et al.  Human immunodeficiency virus within the brains of children with AIDS. , 1990, Clinical neuropathology.

[51]  D. Longo,et al.  Acquired Immunodeficiency Syndrome: Epidemiologic, Clinical, Immunologic, and Therapeutic Considerations , 1984 .

[52]  M. Greaves,et al.  The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus , 1984, Nature.