Macrophage-tropic strains of human immunodeficiency virus type 1 utilize the CD4 receptor

Collman, Ronald G.; Godfrey, Brian; Cutilli, Joann; Rhodes, Audrey; Hassan, Nassef F.; Sweet, Ray; Douglas, Steven D.; Friedman, Harvey M.; Nathanson, Neal; González‐Scarano, Francisco

doi:10.1128/jvi.64.9.4468-4476.1990

Cited by 97 publications

(35 citation statements)

References 57 publications

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“…CCR3 receptor expression is not detected on adult monocytes, concordant with lack of CCR3 mRNA [38]. Both adult [48][49][50] and neonatal [46] monocytes express CD4.…”

Section: Monocytesmentioning

confidence: 87%

The influence of cytokines, chemokines and their receptors on HIV‐1 replication in monocytes and macrophages

Kedzierska

Crowe

Turville

et al. 2002

Reviews in Medical Virology

166

100

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Monocytes, macrophages and dendritic cells play an important role in the initial infection and contribute to its pathogenesis throughout the course of infection. Myeloid cells express CD4 and chemokine receptors known for HIV-1 fusion and entry. The beta-chemokine receptor, CCR5, is the major co-receptor in conjunction with CD4 for macrophage (M)-tropic or (R5) isolates of HIV-1, whereas the alpha-chemokine receptor, CXCR4, facilitates entry of T-tropic or (X4) HIV-1 strains. Cells of myeloid lineage may be infected predominantly with R5- strains, although infection with dual-tropic isolates of HIV-1 (exhibiting the capacity to use CCR-5 and/or CXCR-4 for entry) or some strains of X4- isolates has also been reported. The expression of chemokine receptors, HIV-1 infection and replication is under continuous regulation by a complex cytokine network produced by a variety of cells. The effects of cytokines/chemokines on HIV-1 replication in cells of myeloid lineage can be inhibitory (IFN-alpha, IFN-beta, IFN-gamma, GM-CSF, IL-10, IL-13 and IL-16 and beta-chemokines), stimulatory (M-CSF, TNF-alpha, TNF-beta, IL-1, IL-6) or bifunction al, that is both inhibitory and stimulatory (IL-4). This review focuses on the overall expression of chemokine receptors on cells of myeloid lineage and considers the mechanisms of entry of R5-, X4- and dual-tropic strains of HIV-1 into these cells. The effects of cytokines/chemokines on viral entry and productive HIV-1 infection are also reviewed.

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“…CCR3 receptor expression is not detected on adult monocytes, concordant with lack of CCR3 mRNA [38]. Both adult [48][49][50] and neonatal [46] monocytes express CD4.…”

Section: Monocytesmentioning

confidence: 87%

The influence of cytokines, chemokines and their receptors on HIV‐1 replication in monocytes and macrophages

Kedzierska

Crowe

Turville

et al. 2002

Reviews in Medical Virology

166

100

View full text Add to dashboard Cite

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“…The discovery that HIV-1 used CD4 as the primary receptor for entry defined CD4-expressing cells as targets for HIV-1 [8] but failed to provide a basis for differential infection of the spectra of cells that express CD4 [9]. A mechanistic basis for selective cell tropism by viruses was provided a decade ago by the discovery that the chemokine receptors CCR5 and CXCR4 function as the major entry coreceptors used by M-tropic or T-tropic HIV-1 prototypes, respectively, while D-tropic prototypes could use both coreceptors [10 -12].…”

Section: Target Cell Tropism Vs Coreceptor Utilizationmentioning

confidence: 99%

HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes

Goodenow

Collman

2006

Journal of Leukocyte Biology

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HIV-1 infection of cells is mediated by engagement between viral envelope glycoproteins (Env) and a receptor complex comprising CD4 and one of two chemokine receptors, CCR5 and CXCR4, expressed on the surface of target cells. Most CD4+-transformed T cell lines express only CXCR4, but primary lymphocytes and macrophages, the main cellular targets for infection in vivo, express both coreceptors. Cell- and viral strain-specific utilization of these coreceptor pathways, rather than coreceptor expression per se, regulates lymphocyte and macrophage entry and tropism. Virus use of coreceptor[s] (R5, X4, or R5 and X4) and its target cell tropism (lymphocytes, macrophages, and/or transformed T cell lines) are related but distinct characteristics of Envs. A comprehensive classification schema of HIV-1 Env phenotypes that addresses both tropism and coreceptor use is proposed. Defining Env phenotype based on both parameters is important in the development of entry inhibitors and vaccines, for understanding changes in Env that evolve over time in vivo, and for discerning differences among viral species that underlie aspects of pathogenesis and transmission. Recognizing how tropism is related to, yet differs from, coreceptor selectivity is critical for understanding the mechanisms by which these viral characteristics impact pathogenesis.

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“…[10][11][12][13][14][15] In those cells, expression of CD4 is at considerably lower levels; monocytes express 10-to 20-fold less CD4 than lymphocytes and MDM even less. 16,17 Most notable is that little is known of the structure(s) or functions of the CD4 of nonlymphocytic cells. In contrast to those cells, CD4positive lymphocytes are uniquely equipped with TCR and CD3 receptors and with the CD4 binding TyK, Lck, for recognition of, and response to, presented Ag.…”

Section: Introductionmentioning

confidence: 99%

Marked differences in the structures and protein associations of lymphocyte and monocyte CD4: Resolution of a novel CD4 isoform

et al. 2006

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Summary The structures, molecular interactions and functions of CD4 in a subset of T lymphocytes have been well characterized. The CD4 receptors of other cell types have, however, been poorly documented. We have previously shown that lymphocytes and monocytes/macrophages differ in their expression of CD4 monomers and dimers. In the present study, we have shown further significant differences. Variability in the blocking of CD4 mAb binding by sulfated polyanions indicated differences in exofacial CD4 structures. In contrast to the well-documented 55 kDa monomers in lymphocytic cells, monocytic cells were found to coexpress two monomer isoforms: the 55 kDa form and a novel 59 kDa species. Experimental uncoupling of CD4 disulfides indicated that the oxidized 55 kDa monomer could be converted to the 59 kDa form. This was achieved by chemical reduction of purified native or recombinant CD4, or in cell transfection experiments by mutation of cysteine to alanine in domain 1 (D1) (Cys16 or Cys84) and in domain 4 (D4) (Cys303 or Cys345). All of these modifications promote CD4 distension on SDS-PAGE analysis and indicate that, when CD4 interb-sheet disulfides in the D1 and D4 Ig folds are disrupted, there is an unravelling of the oxidized form to an extended 59 kDa unfolded state. We hypothesize that this may be a transition-state, structural-intermediate in the formation of disulfide-linked homodimers. Also identified were CD4-tyrosine kinase dissimilarities in which lymphocyte CD4 associated with Lck, but monocyte CD4 associated with HcK. These findings show that there is complex heterogeneity in structures and interactions in the CD4 of T lymphocytes and monocytes.

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Macrophage-tropic strains of human immunodeficiency virus type 1 utilize the CD4 receptor

Cited by 97 publications

References 57 publications

The influence of cytokines, chemokines and their receptors on HIV‐1 replication in monocytes and macrophages

The influence of cytokines, chemokines and their receptors on HIV‐1 replication in monocytes and macrophages

HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes

Marked differences in the structures and protein associations of lymphocyte and monocyte CD4: Resolution of a novel CD4 isoform

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