National Centre for Cell Science, Pune University, Ganeshkhind, Pune 411007, India.
J Immunol. 2012 Aug 1;189(3):1431-9. doi: 10.4049/jimmunol.1200946. Epub 2012 Jun 25.
Variola and vaccinia viruses, the two most important members of the family Poxviridae, are known to encode homologs of the human complement regulators named smallpox inhibitor of complement enzymes (SPICE) and vaccinia virus complement control protein (VCP), respectively, to subvert the host complement system. Intriguingly, consistent with the host tropism of these viruses, SPICE has been shown to be more human complement-specific than VCP, and in this study we show that VCP is more bovine complement-specific than SPICE. Based on mutagenesis and mechanistic studies, we suggest that the major determinant for the switch in species selectivity of SPICE and VCP is the presence of oppositely charged residues in the central complement control modules, which help enhance their interaction with factor I and C3b, the proteolytically cleaved form of C3. Thus, our results provide a molecular basis for the species selectivity in poxviral complement regulators.
天花病毒和牛痘病毒是痘病毒科中最重要的两个成员，已知它们分别编码人类补体调节蛋白的同源物，称为天花抑制剂补体酶（SPICE）和牛痘病毒补体控制蛋白（VCP），以颠覆宿主补体系统。有趣的是，与这些病毒的宿主嗜性一致，SPICE 比 VCP 更具有人类补体特异性，而在这项研究中我们表明 VCP 比 SPICE 更具有牛科动物补体特异性。基于诱变和机制研究，我们提出 SPICE 和 VCP 物种选择性转变的主要决定因素是中央补体控制模块中相反电荷残基的存在，这有助于增强它们与因子 I 和 C3b 的相互作用，C3b 是 C3 的蛋白水解形式。因此，我们的研究结果为痘病毒补体调节蛋白的物种选择性提供了分子基础。
