Barrett John W, Sypula Joanna, Wang Fuan, Alston Lindsay R, Shao Zhuhong, Gao Xiujuan, Irvine Timothy S, McFadden Grant
Biotherapeutics Research Group, Robarts Research Institute and Department of Microbiology and Immunology, University of Western Ontario, 1400 Western Road, Room 126, London, ON N6G 2V4, Canada.
J Virol. 2007 Jan;81(1):106-14. doi: 10.1128/JVI.01633-06. Epub 2006 Oct 25.
Myxoma virus (MV) encodes a cell surface protein (M135R) that is predicted to mimic the host alpha/beta interferon receptor (IFN-alpha/beta-R) and thus prevent IFN-alpha/beta from triggering a host antiviral response. This prediction is based on sequence similarity to B18R, the viral IFN-alpha/beta-R from vaccinia virus (VV), which has been demonstrated to bind and inhibit type I interferons. However, M135R is only half the size of VV B18R. All other poxvirus-encoded IFN-alpha/beta-R homologs align only to the amino-terminal half of M135R. Peptide antibodies raised against M135R were used for immunoblotting and immunofluorescence and indicate that M135R is expressed as an early gene and that the product is a cell surface N-linked glycoprotein that is not secreted. In contrast to the predicted properties of M135R as an inhibitor of type I interferon, all binding and inhibition assays designed to demonstrate whether M135R can interact with IFN-alpha/beta have been negative. However, pathogenesis studies with a targeted M135-knockout MV construct (vMyx135KO) indicate that the deletion of M135R severely attenuates MV pathogenesis in the European rabbit. We propose that M135R is an important immunomodulatory virulence factor for myxomatosis but that the target immune ligand is not from the predicted type I interferon family and remains to be identified.
黏液瘤病毒（MV）编码一种细胞表面蛋白（M135R），据预测该蛋白可模拟宿主α/β干扰素受体（IFN-α/β-R），从而阻止IFN-α/β触发宿主抗病毒反应。这一预测基于与痘苗病毒（VV）的病毒IFN-α/β-R即B18R的序列相似性，B18R已被证明能结合并抑制I型干扰素。然而，M135R的大小仅为VV B18R的一半。所有其他痘病毒编码的IFN-α/β-R同源物仅与M135R的氨基末端一半序列对齐。针对M135R产生的肽抗体用于免疫印迹和免疫荧光分析，结果表明M135R作为早期基因表达，其产物是一种不分泌的细胞表面N-连接糖蛋白。与M135R作为I型干扰素抑制剂的预测特性相反，所有旨在证明M135R是否能与IFN-α/β相互作用的结合和抑制试验均为阴性。然而，对靶向M135基因敲除的MV构建体（vMyx135KO）进行的发病机制研究表明，M135R的缺失严重减弱了MV在欧洲兔中的致病作用。我们认为M135R是黏液瘤病重要的免疫调节毒力因子，但靶免疫配体并非来自预测的I型干扰素家族，仍有待确定。
