Symons Julian A, Tscharke David C, Price Nicola, Smith Geoffrey L
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
J Gen Virol. 2002 Aug;83(Pt 8):1953-1964. doi: 10.1099/0022-1317-83-8-1953.
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.
痘苗病毒（VV）西储株基因B8R编码一种43 kDa的糖蛋白，该蛋白在感染早期以同二聚体形式从受感染细胞中分泌出来。这种蛋白与细胞干扰素-γ受体（IFN-γR）的胞外结构域具有氨基酸相似性，能结合并抑制多种物种的干扰素-γ。在此我们证明B8R蛋白也能抑制马的干扰素-γ。通过引物延伸分析确定了B8R mRNA的5′端，并通过构建缺失B8R基因的缺失突变体（vDeltaB8R）和将B8R基因重新插入缺失突变体中的回复病毒（vB8R-R），研究了IFN-γR对VV毒力的影响。还构建并研究了一种表达小鼠IFN-γR可溶性形式的重组病毒。在啮齿动物感染模型中测试了这些病毒的毒力。在小鼠中，与野生型和回复病毒相比，VV IFN-γR的缺失不影响毒力，这与VV IFN-γR对小鼠干扰素-γ的低亲和力一致。然而，小鼠可溶性IFN-γR的表达略微增加了病毒毒力。在兔皮肤中，与野生型和回复病毒相比，VV IFN-γR的缺失产生了具有组织学差异的病变。最后，通过表面等离子体共振测定了VV IFN-γR对人和小鼠干扰素-γ的亲和常数。
