Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri.
Viruses are known to acquire and modify the genes of their hosts to attain a survival advantage in the host environment. Herpesvirus saimiri (HVS) is a T-lymphotropic virus that causes fatal lymphoproliferative diseases in several non-human primates. The gene ECRF3 of HVS was most likely acquired from a primate host. ECRF3 encodes a putative seven-transmembrane-domain receptor that is remotely related (approximately 30% amino acid identity) to the known mammalian alpha and beta chemokine receptors, namely interleukin-8 receptor (IL8R) types A and B and the MIP-1 alpha/RANTES receptor, respectively. Chemokines regulate the trafficking, activation, and, in some cases, proliferation of myeloid and lymphoid cell types. We now show that ECRF3 encodes a functional receptor for the alpha chemokines IL-8, GRO/melanoma growth stimulatory activity (MGSA), and NAP-2 but not for beta chemokines, a specificity identical to that of IL8RB. Paradoxically, IL8RA shares 77% amino acid identity with IL8RB but is not a receptor for GRO/MGSA or NAP-2. This is the first functional characterization of a viral seven-transmembrane-domain receptor. It suggests a novel role for alpha chemokines in the pathogenesis of HVS infection by transmembrane signaling via the product of ECRF3.
Ahuja
S K
SK
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Murphy
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics*; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D018123:Receptors, Interleukin / Q000235:genetics*; D023062:Receptors, Interleukin-8A; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000235:genetics*; D014981:Xenopus
D016207:Cytokines; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D014764:Viral Proteins