Human immunodeficiency virus type-1 and chemokines: beyond competition for common cellular receptors

Stantchev, Tzanko S.; Broder, Christopher C.

doi:10.1016/s1359-6101(00)00033-2

Cited by 68 publications

(63 citation statements)

References 253 publications

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“…3, B and C). This differential effect would suggest qualitative differences in SDF-1 and gp120-mediated signaling, possibly because gp120 also binds and transduces signals through CD4 (9). How CXCR4-and CD4-dependent pathways intersect requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes

Balabanian

Harriague

Décrion

et al. 2004

The Journal of Immunology

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Interaction of HIV-1 envelope glycoprotein gp120 with the chemokine receptor CXCR4 triggers not only viral entry but also an array of signal transduction cascades. Whether gp120 induces an incomplete or aberrant set of signals, or whether it can function as a full CXCR4 agonist, remains unclear. We report that, in unstimulated human primary CD4+ T cells, the spectrum of signaling responses induced by gp120 through CXCR4 paralleled that induced by the natural ligand stromal cell-derived factor 1/CXCL12. gp120 activated heterotrimeric G proteins and the major G protein-dependent pathways, including calcium mobilization, phosphoinositide-3 kinase, and Erk-1/2 MAPK activation. Interestingly, gp120 caused rapid actin cytoskeleton rearrangements and profuse membrane ruffling, as evidenced by dynamic confocal imaging. This coordinated set of events resulted in a bona fide chemotactic response. Inactivated HIV-1 virions that harbored conformationally intact envelope glycoproteins also caused actin polymerization and chemotaxis, while similar virions devoid of envelope glycoproteins did not. Thus gp120, in monomeric as well as oligomeric, virion-associated form, elicited a complex cellular response that mimicked the effects of a chemokine. HIV-1 has therefore the capacity to dysregulate the vast CD4+ T cell population that expresses CXCR4. In addition, HIV-1 may exploit its chemotactic properties to retain potential target cells and locally perturb their cytoskeleton, thereby facilitating viral transmission.

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Section: Discussionmentioning

confidence: 99%

CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes

Balabanian

Harriague

Décrion

et al. 2004

The Journal of Immunology

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“…Other transcription factors and protein kinases, including c-jun, JNK, MEK, p38 MAPK, STAT, and JAK, all of which participate in antigen-specific T cell activation (14,15,32), were induced ( Figs. 1 and 2, Table 1).…”

Section: Relevant Transcription Factors and Kinases Induced By Hiv-1 mentioning

confidence: 99%

“…It has been suggested that HIV gp120 also facilitates replication in suboptimally activated cells (12)(13)(14)(15). Gp120 transduces near-simultaneous signals through CD4 (16), a component of the T cell receptor complex, and CCR5, a chemokine receptor (17)(18)(19).…”

mentioning

confidence: 99%

HIV envelope induces a cascade of cell signals in non-proliferating target cells that favor virus replication

Cicala

Arthos

Selig

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

154

147

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Certain HIV-encoded proteins modify host-cell gene expression in a manner that facilitates viral replication. These activities may contribute to low-level viral replication in nonproliferating cells. Through the use of oligonucleotide microarrays and high-throughput Western blotting we demonstrate that one of these proteins, gp120, induces the expression of cytokines, chemokines, kinases, and transcription factors associated with antigen-specific T cell activation in the absence of cellular proliferation. Examination of transcriptional changes induced by gp120 in freshly isolated peripheral blood mononuclear cells and monocyte-derivedmacrophages reveals a broad and complex transcriptional program conducive to productive infection with HIV. Observations include the induction of nuclear factor of activated T cells, components of the RNA polymerase II complex including TFII D, proteins localized to the plasma membrane, including several syntaxins, and members of the Rho protein family, including Cdc 42. These observations provide evidence that envelope-mediated signaling contributes to the productive infection of HIV in suboptimally activated T cells.H IV preferentially replicates in proliferating CD4 ϩ T cells(1). However recent evidence suggests that, in vivo, resting and suboptimally activated T cells may serve as targets for low-level productive infection in the absence of cellular proliferation (2-5). Infection in this manner may contribute to the establishment and͞or maintenance of persistent viral reservoirs that currently prevent the eradication of virus. To productively infect suboptimally activated CD4 ϩ T cells, HIV must overcome post-entry barriers to replication (6-8).DNA microarrays have been used to characterize the effect of HIV on target cell transcription (9, 10); in one microarray-based study, HIV Nef was shown to diminish barriers to viral replication by mimicking antigen-specific T cell proliferation signals (11,12). It has been suggested that HIV gp120 also facilitates replication in suboptimally activated cells (12-15). Gp120 transduces near-simultaneous signals through CD4 (16), a component of the T cell receptor complex, and CCR5, a chemokine receptor (17)(18)(19). In vivo concentrations of gp120 (20, 21) fall within the range required to induce signaling in vitro (17)(18)(19)22). To provide a more complete picture of the complex cascade of signals induced by gp120, we treated freshly isolated peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) with an envelope derived from a CCR5-using virus and measured temporal changes in the levels of mRNA by using Affymetrix (Santa Clara, CA) U95A oligonucleotide microarrays that include probes encompassing Ϸ12,600 genes. In addition, we used a high-throughput Western blot analysis that allowed us to screen protein lysates with 800 monoclonal antibodies. The gp120 used was derived from JR-FL, a CCR5-tropic molecular clone obtained from a minimally passaged viral isolate (23). We used concentrations of envelope near or bel...

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“…The chemokines are a family of pro-inflammatory cytokines that act through 19 different G protein-coupled receptors to regulate numerous routine physiological and pathophysiological processes [1,2]. Chemokines are classified into four subfamilies according to the patterns of conserved cysteines in their amino acid sequences.…”

Section: Introductionmentioning

confidence: 99%

Differential chemokine activation of CC chemokine receptor 1‐regulated pathways: ligand selective activation of Gα ₁₄‐coupled pathways

et al. 2004

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Chemokines regulate the chemotaxis, development, and differentiation of many cell types enabling the regulation of routine immunosurveillance and immunological adaptation. CC chemokine receptor 1 (CCR1) is the target of 11 chemokines. This promiscuity of receptorligand interactions and the potential for functional redundancy has led us to investigate the selective activation of CCR1-coupled pathways by known CCR1 agonists. Chemokines leukotactin-1, macrophage inflammatory protein (MIP)-1 § , monocyte chemotactic peptide (MCP)-3, RANTES, and MIP-1ˇall inhibited adenylyl cyclase activity in cells transiently transfected with CCR1. In contrast, only MIP-1ˇwas unable to signal via G 14 -, G 16 -or chimeric 16z44-coupled pathways. In a stable cell line expressing CCR1 and G § 14 , all of these five chemokines along with hemofiltrate CC chemokine (HCC)-1 and myeloid progenitor inhibitory factor (MPIF)-1 were able to stimulate G i/o -coupled pathways, but MIP-1ˇ, HCC-1 and MPIF-1 were unable to activate G 14 -mediated stimulation of phospholipase C g activity. In addition, MIP-1ˇwas unable to promote the phosphorylation of extracellular signalregulated kinase and c-Jun N-terminal kinase. This suggests that different chemokines are able to selectively activate CCR1-coupled pathways, probably because of different intrinsic ligand efficacies. CCR1 and G § 14 or G § 16 are co-expressed in several cell types and we hypothesize that selective activation of chemokine receptors provides a mechanism by which chemokines are able to fine-tune intracellular signaling pathways.

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Human immunodeficiency virus type-1 and chemokines: beyond competition for common cellular receptors

Cited by 68 publications

References 253 publications

CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes

CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes

HIV envelope induces a cascade of cell signals in non-proliferating target cells that favor virus replication

Differential chemokine activation of CC chemokine receptor 1‐regulated pathways: ligand selective activation of Gα ₁₄‐coupled pathways

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Human immunodeficiency virus type-1 and chemokines: beyond competition for common cellular receptors

Cited by 68 publications

References 253 publications

CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes

CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes

HIV envelope induces a cascade of cell signals in non-proliferating target cells that favor virus replication

Differential chemokine activation of CC chemokine receptor 1‐regulated pathways: ligand selective activation of Gα 14‐coupled pathways

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Differential chemokine activation of CC chemokine receptor 1‐regulated pathways: ligand selective activation of Gα ₁₄‐coupled pathways