Human cytomegalovirus open reading frame US28 encodes a functional beta chemokine receptor

• Published in: The Journal of biological chemistry Vol. 269; no. 46; pp. 28539 - 28542
• Main Authors: Gao, J L, Murphy, P M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.11.1994; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Cell Line; Cloning, Molecular; Cytomegalovirus - genetics; Genes, Viral; Humans; Molecular Sequence Data; Open Reading Frames; Receptors, CCR2; Receptors, CCR5; Receptors, Chemokine; Receptors, Cytokine - genetics; Receptors, Immunologic - genetics; Sequence Homology, Amino Acid; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)61936-8

Human cytomegalovirus infects epithelial, smooth muscle, and white blood cells in vivo causing acute, latent, and chronic infections. A data base search revealed that the amino acid sequence of the putative protein encoded by open reading frame US28 of human cytomegalovirus is approximately 30% identical to those of the mammalian leukocyte receptors for alpha and beta chemokines. This suggested that US28 was originally copied from a human chemokine receptor gene, perhaps to provide the virus with a selective advantage through molecular mimicry. Chemokines regulate the trafficking and activation of mammalian leukocytes and activate calcium-mobilizing, heptahelical, G protein-coupled receptors. We now show that US28 encodes a promiscuous calcium-mobilizing receptor for the beta chemokines RANTES (regulated upon activation, normal T expressed and secreted), macrophage inflammatory protein-1 alpha, and monocyte chemoattractant protein-1, but not for the alpha chemokines interleukin-8 or gamma IP10. The chemokine selectivity of the US28 product is distinct from that of known mammalian beta chemokine receptors. This finding suggests a role for beta chemokines in the pathogenesis of human cytomegalovirus infection by transmembrane signaling via the product of US28.