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Viral Chemokine Receptors

P. Murphy

Published 2015 in Frontiers in Immunology

ABSTRACT

When my lab sequenced the first chemokine receptors CXCR2 and CCR1 in 1991, the top BLAST hit for CCR1 was open reading frame (ORF) US28 of human cytomegalovirus (HCMV), indicating an obvious common ancestor and a possible example of gene piracy. Pox virologists had already identified virally encoded TNF and IFN-γ binding proteins, copied from the host and redeployed as cytokine scavengers and immune evasion factors; however, there were no precedents for G protein-coupled receptors in viruses or signaling viral immunoreceptor homologs. Tom Schall, then at Genentech, who had candidate CC chemokine receptor clones, learned about our CCR1 discovery and proposed a collaboration. I told him about the key features of CCR1: its specificity for CCL3 and CCL5, as well as monocytes and lymphocytes, and its sequence homology to US28 (1); however, he eventually wanted to pursue CCR1 independently, and published it in Cell in fall, 1992 along with data that US28 could bind to CCL2, CCL3, CCL4, and CCL5. A month earlier, our paper had been rejected by Cell for lack of sufficient binding data; however, we eventually published our paper in early 1993 in the Journal of Experimental Medicine (1), and the NIH received the patent for cloning CCR1.

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