A study of the vaccinia virus interferon-gamma receptor and its contribution to virus virulence.
Vaccinia virus (VV) strain Western Reserve gene B8R encodes a 43 kDa glycoprotein that is secreted from infected cells early in infection as a homodimer. This protein has amino acid similarity with the extracellular domain of cellular IFN-gamma receptor (IFN-gammaR) and binds and inhibits IFN-gamma from a wide range of species. Here we demonstrate that the B8R protein also inhibits equine IFN-gamma. The 5' end of the B8R mRNA has been mapped by primer extension analysis and the contribution of IFN-gammaRs to VV virulence was studied by the construction of a deletion mutant lacking the B8R gene (vDeltaB8R) and a revertant virus (vB8R-R) in which the B8R gene was re-inserted into the deletion mutant. A recombinant virus that expressed a soluble form of the mouse IFN-gammaR was also constructed and studied. The virulence of these viruses was tested in rodent models of infection. In mice, the loss of the VV IFN-gammaR did not affect virulence compared with WT and revertant viruses, consistent with the low affinity of the VV IFN-gammaR for mouse IFN-gamma. However, expression of the mouse soluble IFN-gammaR increased virus virulence slightly. In rabbit skin, loss of the VV IFN-gammaR produced lesions with histological differences compared with WT and revertant viruses. Lastly, the affinity constants of the VV IFN-gammaR for human and mouse IFN-gamma were determined by surface plasmon resonance.
Symons
Julian A
JA
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
Tscharke
David C
DC
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
Price
Nicola
N
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
Smith
Geoffrey L
GL
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006736:Horses; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011817:Rabbits; D017471:Receptors, Interferon / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D012995:Solubility; D014615:Vaccinia / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor