HHV8-encoded vMIP-I Selectively Engages Chemokine Receptor CCR8

Dairaghi, Daniel J.; Fan, Rong A.; McMaster, Brian E.; Hanley, Michael R.; Schall, Thomas J.

doi:10.1074/jbc.274.31.21569

Cited by 184 publications

(121 citation statements)

References 26 publications

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“…The threonine 10/12 and tyrosine 14/15 pairs are conserved between human and murine CCR8, but the human protein is two amino acid residues longer than the murine form, with a threonine at position 9 and a tyrosine at position 13 that are putative substrates for modification. This probably adds complexity to the potential post-translational modifications in human CCR8 and may explain the discrepancy in reports on mouse CCL1 activity with human CCR8 (8,10,28,29).…”

Section: Discussionmentioning

confidence: 58%

Analysis of Post-translational CCR8 Modifications and Their Influence on Receptor Activity

Gutiérrez

Kremer

Zaballos

et al. 2004

Journal of Biological Chemistry

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Post-translational modifications of the extracellular portions of receptors located in the cell membrane can contribute to modulating their biological activity. Using a mutagenesis approach in which single or multiple Tyrto-Phe, Thr-to-Ala, Ser-to-Ala, and Asn-to-Gln substitutions were made at the appropriate positions, we analyzed the sulfation and glycosylation state of the murine CCR8 chemokine receptor, and the way in which these post-translational modifications affect CCR8 activity. A Y14Y15-to-F14F15 CCR8 mutant was less sulfated than the wild-type receptor. An N8-to-Q8 mutant was less glycosylated than wild-type, and a double T10T12-to-A10A12 mutant showed even less glycosylation. We established a flow cytometric analysis with an Fc-fused form of mouse CCL1 to determine precisely the ligandbinding activity of these mutants. Single mutants at amino acid positions 8, 10 or 12 bound CCL1-Fc similarly to wild-type CCR8, whereas the F14F15 double mutant was essentially inactive and the A10A12 double mutant showed about 65% of wild-type ligand-binding activity. Calcium flux activity assays were performed with these mutants, yielding results consistent with those from the ligand binding assays. These data indicate that sulfation at specific positions of the N-terminal domain of mouse CCR8 is critical for its biological activity, whereas glycosylation has a minor influence.

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Section: Discussionmentioning

confidence: 58%

Analysis of Post-translational CCR8 Modifications and Their Influence on Receptor Activity

Gutiérrez

Kremer

Zaballos

et al. 2004

Journal of Biological Chemistry

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“…The existence of these virus-encoded homologues of cellular proteins is indirect evidence of their relevant role in orchestrating the host immune response to invading pathogens (62). Many large DNA viruses, e.g., human herpes viruses, including CMV and HHV-8, as well as the poxvirus molluscum contagiosum, encode several ␤-chemokine homologues (virokines) acting on CCR3 or CCR8 receptors (63)(64)(65)(66)(67)(68). HIV-1 Tat protein is the first identified virokine encoded by retrovirus that is functionally active on human Fc⑀RI ϩ cells through the interaction with CCR3 receptor.…”

Section: Discussionmentioning

confidence: 99%

Tat Protein Is an HIV-1-Encoded β-Chemokine Homolog That Promotes Migration and Up-Regulates CCR3 Expression on Human FcεRI+ Cells

Paulis

Palma

Gioia

et al. 2000

The Journal of Immunology

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Human basophils and mast cells express the chemokine receptor CCR3, which binds the chemokines eotaxin and RANTES. HIV-1 Tat protein is a potent chemoattractant for basophils and lung mast cells obtained from healthy individuals seronegative for Abs to HIV-1 and HIV-2. Tat protein induced a rapid and transient Ca2+ influx in basophils and mast cells, analogous to β-chemokines. Tat protein neither induced histamine release from human basophils and mast cells nor increased IL-3-stimulated histamine secretion from basophils. The chemotactic activity of Tat protein was blocked by preincubation of FcεRI+ cells with anti-CCR3 Ab. Preincubation of Tat with a mAb anti-Tat (aa 1–86) blocked the migration induced by Tat. In contrast, a mAb specific for the basic region (aa 46–60) did not inhibit the chemotactic effect of Tat protein. Tat protein or eotaxin desensitized basophils to a subsequent challenge with the autologous or the heterologous stimulus. Preincubation of basophils with Tat protein up-regulated the level of CCR3 mRNA and the surface expression of the CCR3 receptor. Tat protein is the first identified HIV-1-encoded β-chemokine homologue that influences the directional migration of human FcεRI+ cells and the expression of surface receptor CCR3 on these cells.

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“…120,121 Virally encoded proteins have been identified that bind chemokines and could be a means of achieving chemokine blockade. 122,123 This blockade can easily be attained using peptide transduction domains fused to recombinant proteins or short oligonucleotides, especially if administered during procurement and reperfusion of the donor pancreas. However, long-term expression of some of these molecules may have a greater effect on graft survival once stable gene expression is achieved.…”

Section: Insulin Replacement Strategiesmentioning

confidence: 99%