Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates. 1999

A V Albright, and J T Shieh, and T Itoh, and B Lee, and D Pleasure, and M J O'Connor, and R W Doms, and F González-Scarano
Departments of Neurology and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

Microglia are the main human immunodeficiency virus (HIV) reservoir in the central nervous system and most likely play a major role in the development of HIV dementia (HIVD). To characterize human adult microglial chemokine receptors, we analyzed the expression and calcium signaling of CCR5, CCR3, and CXCR4 and their roles in HIV entry. Microglia expressed higher levels of CCR5 than of either CCR3 or CXCR4. Of these three chemokine receptors, only CCR5 and CXCR4 were able to transduce a signal in microglia in response to their respective ligands, MIP-1beta and SDF-1alpha, as recorded by single-cell calcium flux experiments. We also found that CCR5 is the predominant coreceptor used for infection of human adult microglia by the HIV type 1 dementia isolates HIV-1DS-br, HIV-1RC-br, and HIV-1YU-2, since the anti-CCR5 antibody 2D7 was able to dramatically inhibit microglial infection by both wild-type and single-round luciferase pseudotype reporter viruses. Anti-CCR3 (7B11) and anti-CXCR4 (12G5) antibodies had little or no effect on infection. Last, we found that virus pseudotyped with the DS-br and RC-br envelopes can infect cells transfected with CD4 in conjunction with the G-protein-coupled receptors APJ, CCR8, and GPR15, which have been previously implicated in HIV entry.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015526 AIDS Dementia Complex A neurologic condition associated with the ACQUIRED IMMUNODEFICIENCY SYNDROME and characterized by impaired concentration and memory, slowness of hand movements, ATAXIA, incontinence, apathy, and gait difficulties associated with HIV-1 viral infection of the central nervous system. Pathologic examination of the brain reveals white matter rarefaction, perivascular infiltrates of lymphocytes, foamy macrophages, and multinucleated giant cells. (From Adams et al., Principles of Neurology, 6th ed, pp760-1; N Engl J Med, 1995 Apr 6;332(14):934-40) AIDS Encephalopathy,Dementia Complex, AIDS-Related,HIV Dementia,HIV Encephalopathy,HIV-1-Associated Cognitive Motor Complex,HIV-Associated Cognitive Motor Complex,AIDS-Related Dementia Complex,Acquired-Immune Deficiency Syndrome Dementia Complex,Dementia Complex, Acquired Immune Deficiency Syndrome,Encephalopathy, AIDS,Encephalopathy, HIV,HIV-1 Cognitive and Motor Complex,AIDS Encephalopathies,AIDS Related Dementia Complex,Complex, AIDS Dementia,Complex, AIDS-Related Dementia,Dementia Complex, AIDS,Dementia Complex, AIDS Related,Dementia, HIV,Dementias, HIV,Encephalopathies, AIDS,Encephalopathies, HIV,HIV 1 Associated Cognitive Motor Complex,HIV 1 Cognitive and Motor Complex,HIV Associated Cognitive Motor Complex,HIV Dementias,HIV Encephalopathies
D015728 Receptors, HIV Cellular receptors that bind the human immunodeficiency virus that causes AIDS. Included are CD4 ANTIGENS, found on T4 lymphocytes, and monocytes/macrophages, which bind to the HIV ENVELOPE PROTEIN GP120. AIDS Virus Receptors,HIV Receptors,HTLV-III Receptors,Receptors, AIDS Virus,Receptors, HTLV-III,HTLV III Receptors,Receptors, HTLV III,Virus Receptors, AIDS
D017628 Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Microglial Cell,Cell, Microglial,Microglial Cells,Microglias
D054397 Receptors, CCR3 CCR receptors with specificity for CHEMOKINE CCL11 and a variety of other CC CHEMOKINES. They are expressed at high levels in T-LYMPHOCYTES; EOSINOPHILS; BASOPHILS; and MAST CELLS. Antigens, CD193,CC Chemokine Receptor 3,CCR3 Receptors,CD193 Antigens,CC CKR3,CC Chemokine Receptors 3,CCR3 Receptor,Receptor, CCR3
D054407 Chemokine CCL4 A CC chemokine with specificity for CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES and a variety of other immune cells. This chemokine is encoded by multiple genes. CCL4 Chemokine,CCL4L1 Chemokine,CCL4L2 Chemokine,Chemokine CCL4L1,Chemokine CCL4L2,MIP-1beta,Macrophage Inflammatory Protein 1-beta,Macrophage Inflammatory Protein-1beta2,CCL4, Chemokine,CCL4L1, Chemokine,CCL4L2, Chemokine,Chemokine, CCL4,Chemokine, CCL4L1,Chemokine, CCL4L2,Inflammatory Protein-1beta2, Macrophage,MIP 1beta,Macrophage Inflammatory Protein 1 beta,Macrophage Inflammatory Protein 1beta2
D018946 Chemokine CCL5 A CC-type chemokine that is a chemoattractant for EOSINOPHILS; MONOCYTES; and LYMPHOCYTES. It is a potent and selective eosinophil chemotaxin that is stored in and released from PLATELETS and activated T-LYMPHOCYTES. Chemokine CCL5 is specific for CCR1 RECEPTORS; CCR3 RECEPTORS; and CCR5 RECEPTORS. The acronym RANTES refers to Regulated on Activation, Normal T Expressed and Secreted. CCL5 Chemokine,RANTES,RANTES Protein, T-Cell,CCL5, Chemokine,Chemokine, CCL5,RANTES Protein, T Cell,T-Cell RANTES Protein
D019402 Macrophage Inflammatory Proteins Heparin-binding proteins that exhibit a number of inflammatory and immunoregulatory activities. Originally identified as secretory products of MACROPHAGES, these chemokines are produced by a variety of cell types including NEUTROPHILS; FIBROBLASTS; and EPITHELIAL CELLS. They likely play a significant role in respiratory tract defenses. Macrophage Inflammatory Protein,Macrophage Inflammatory Protein-1,Inflammatory Protein, Macrophage,Inflammatory Protein-1, Macrophage,Inflammatory Proteins, Macrophage,Macrophage Inflammatory Protein 1,Protein, Macrophage Inflammatory,Protein-1, Macrophage Inflammatory

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