Yaba-like disease virus chemokine receptor 7L, a CCR8 orthologue.
Yaba-like disease virus (YLDV) gene 7L encodes a seven-transmembrane G protein-coupled receptor with 53 % amino acid identity to human CC chemokine receptor 8 (CCR8). Initial characterization of 7L showed that this 56 kDa cell-surface glycoprotein binds human CCL1 with high affinity (Kd=0.6 nM) and induces signal transduction by activation of heterotrimeric G proteins and downstream protein kinases. Further characterization of YLDV 7L is presented here and shows that murine CC chemokines can induce G-protein activation via the 7L receptor, despite having a low binding affinity for this receptor. In addition, when expressed by recombinant vaccinia virus (VACV), YLDV 7L was found on the outer envelope of VACV extracellular enveloped virus. The contribution of 7L to poxvirus pathogenesis was investigated by infection of mice with a recombinant VACV expressing 7L (vDeltaB8R-7L) and was compared with the outcome of infection by parental and revertant control viruses. In both intranasal and intradermal models, expression of 7L caused attenuation of VACV. The role of this protein in viral virulence is discussed.
Najarro
Pilar
P
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Gubser
Caroline
C
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Hollinshead
Michael
M
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Fox
James
J
Department of Leukocyte Biology, Faculty of Medicine, Imperial College London, South Kensington Campus, Exhibition Road, London SW1 2AZ, UK.
Pease
James
J
Department of Leukocyte Biology, Faculty of Medicine, Imperial College London, South Kensington Campus, Exhibition Road, London SW1 2AZ, UK.
Smith
Geoffrey L
GL
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
D000281:Administration, Intranasal; D000818:Animals; D002460:Cell Line; D019742:Chemokines, CC / Q000378:metabolism*; D006801:Humans; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000737:chemistry*; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011995:Recombination, Genetic; D015398:Signal Transduction; D014615:Vaccinia / Q000473:pathology / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014771:Virion / Q000378:metabolism; D014774:Virulence; D018158:Yatapoxvirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
C103330:CCR8 protein, human; D019742:Chemokines, CC; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D011991:Receptors, Virus