CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia

  title={CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia},
  author={Jianglin He and Youzhi Chen and M. Farzan and Hyeryun Choe and Asa Ohagen and Suzanne Gartner and Jorge A. Busciglio and Xiaoyu Yang and Wolfgang Hofmann and Walter Newman and Charles Reay Mackay and Joseph G. Sodroski and Dana Gabuzda},
Several members of the chemokine receptor family are used together with CD4 for HIV-1 entry into target cells1–6. T cell line-tropic (T-tropic) HIV-1 viruses use the chemokine receptor CXCR4 as a co-receptor1, whereas macrophage-tropic (M-tropic) primary viruses use CCR5 (refs 2–6). Individuals with defective CCR5 alleles exhibit resistance to HIV-1 infection7,8, suggesting that CCR5 has an important role in vivo in HIV-1 replication. A subset of primary viruses can use CCR3 as well as CCR5 as… 

Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS.

Findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication.

Co‐receptor use by HIV and inhibition of HIV infection by chemokine receptor ligands

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Role of the β-Chemokine Receptors CCR3 and CCR5 in Human Immunodeficiency Virus Type 1 Infection of Monocytes and Microglia

The importance of mononuclear phagocyte heterogeneity in establishing HIV-1 infection and persistence is demonstrated, as well as the importance of chemokine receptors for infection of these cells, which are necessary coreceptors for HIV- 1 entry.

Chemokine receptors and mechanisms of cell death in HIV neuropathogenesis.

Understanding the role of CXCR4 and other chemokine receptors in HIV-1 neuropathogenesis will help to advance the development of new therapeutic strategies for the prevention and treatment of neurologic disorders associated with HIV- 1 infection.

Determinants of HIV-1 Coreceptor Function on CC Chemokine Receptor 3

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Chemokine receptors and virus entry in the central nervous system.

Understanding the role ofChemokine receptors and their chemokine ligands in HIV-1 and SIV infection of the CNS will elucidate mechanisms of viral tropism and pathogenesis and advance the development of new therapeutic strategies.

Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry.

The presence of multiple chemokine receptors on dendritic cells (DC) that may function as coreceptors for HIV entry is identified and identified, providing evidence for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T-tropic strains of HIV.

gp120 Induces Cell Death in Human Neuroblastoma Cells Through the CXCR4 and CCR5 Chemokine Receptors

In this study, insight is gained into the mechanism(s) of neurotoxicity elicited by the viral glycoprotein using the human neuroblastoma CHP100 cell line as an experimental model and suggests that the neuronal injury observed in HIV‐1 infection could be due to direct (or indirect) interactions between the viral protein gp120 and chemokine and/or NMDA receptors.

Receptors Used as Coreceptors for HIV Entry Dendritic Cells Express Multiple Chemokine

The presence of multiple chemokine receptors on dendritic cells (DC) that may function as coreceptors for HIV entry is identified, providing evidence for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T-tropic strains of HIV.



Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene

It is shown that a mutant allele of CCR-5 is present at a high frequency in caucasian populations, but is absent in black populations from Western and Central Africa and Japanese populations, and a 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains.

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The β-chemokines MIP-1α, MIP-1β and RANTES inhibit infection of CD4+ cells by primary, non-syncytium-inducing (NSI) HIV-1 strains at the virus entry stage, and also block env-mediated cell–cell

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It is proposed that at least one determinant for mononuclear phagocyte tropism involves target cell interactions with regions of gp120 distinct from the CD4-binding domain, and genetic mapping of the macrophage-tropic phenotype by construction of recombinant viruses indicates this region can be determined by a 157-amino-acid region of the gp120 glycoprotein of HIV-1JR–FL.

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The identification of a human chemokine of the CXC type, stromal cell-derived factor 1 (SDF-1), as the natural ligand for LESTR/fusin, and the term CXCR-4 is proposed for this receptor, in keeping with the new Chemokine-receptor nomenclature.

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The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry

Testing of potential receptors demonstrated that SDF-1 signalled through, and hence 'adopted', the orphan receptor LESTR, which is therefore designated CXC-chemokine receptor-4 (CXCR-4).

Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells

Recombinant human RANTES, Mip-1α, and MIP-1β induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) and may have relevance for the prevention and therapy of AIDS.

Identification of a major co-receptor for primary isolates of HIV-1

The principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR-5, a receptor for the β-chemokines RANTES, Mip-1α and MIP-1β.