Work

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

Year: 1994

Type: article

Abstract: 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.

Source: Journal of Biological Chemistry

DOI: 10.1016/s0021-9258(19)61936-8

Authors: J L Gao, P M Murphy

Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases

Language: English

Topic: Chemokine receptors and signaling

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430