Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8, a virus that appears to be involved in the pathogenesis of Kaposi's sarcoma and primary effusion lymphomas, encodes a G protein-coupled receptor (KSHV-GPCR) that exhibits constitutive signaling. In this report, we show that two chemokines, interleukin 8 (IL-8) and growth-related protein-alpha, activate KSHV-GPCR over constitutive levels. Moreover, as with human receptors, the integrity of the ELR motif of these chemokines is required for activation of KSHV-GPCR. Other residues that are required for IL-8 binding to human chemokine receptors CXCR1 and CXCR2 are important for KSHV-GPCR activation also. Thus, it appears that the ELR binding site and other key domains of ELR chemokine activation have been preserved in the virus KSHV-GPCR. The results suggest that KSHV-GPCR originated from CXCR1 or CXCR2 and that activation of KSHV-GPCR by endogenous chemokines may affect the pathobiology of KSHV infection in humans.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Binding Sites
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COS Cells
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Chemokine CXCL1
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Chemokine CXCL10
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Chemokines / pharmacology*
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Chemokines, CXC / pharmacology
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Chemotactic Factors / pharmacology
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Dose-Response Relationship, Drug
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GTP-Binding Proteins / metabolism
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Growth Substances / pharmacology
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Herpesvirus 8, Human*
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Intercellular Signaling Peptides and Proteins*
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Interleukin-8 / pharmacology
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Mice
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Molecular Sequence Data
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Oligopeptides / pharmacology
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Platelet Factor 4 / pharmacology
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Protein Binding
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Receptors, Chemokine / genetics
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Receptors, Chemokine / metabolism*
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Recombinant Proteins / metabolism
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Signal Transduction
Substances
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CXCL1 protein, human
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Chemokine CXCL1
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Chemokine CXCL10
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Chemokines
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Chemokines, CXC
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Chemotactic Factors
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Cxcl1 protein, mouse
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G protein-coupled receptor, Human herpesvirus 8
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Growth Substances
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Intercellular Signaling Peptides and Proteins
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Interleukin-8
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Oligopeptides
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Receptors, Chemokine
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Recombinant Proteins
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Platelet Factor 4
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GTP-Binding Proteins