Huemer H P, Wang Y, Garred P, Koistinen V, Oppermann S
Institute for Hygiene, University of Innsbruck, Austria.
Immunology. 1993 Aug;79(4):639-47.
Herpes simplex virus (HSV) encodes a protein, glycoprotein C (gC), which binds to the third complement component, the central mediator of complement activation. In this study the structural and functional relationships of gC from HSV type 1 (HSV-1) and known human complement regulatory proteins factor H, properdin, factor B, complement receptor 1 (CR1) and 2 (CR2) were investigated. The interaction of gC with C3b was studied using purified complement components, synthetic peptides, antisera against different C3 fragments and anti-C3 monoclonal antibodies (mAb) with known inhibitory effects on C3-ligand interactions. All the mAb that inhibited gC/C3b interactions, in a differential manner, also prevented binding of C3 fragments to factors H, B, CR1 or CR2. No blocking was observed with synthetic peptides representing different C3 regions or with factor B and C3d, whereas C3b, C3c and factor H were inhibitory, as well as purified gC. There was no binding of gC to cobra venom factor (CVF), a C3c-like fragment derived from cobra gland. Purified gC bound to iC3, iC3b and C3c, but failed to bind to C3d. Glycoprotein C bound only weakly to iC3 derived from bovine and porcine plasma, thus indicating a preference of the viral protein for the appropriate host. Binding of gC was also observed to proteolytic C3 fragments, especially to the beta-chain, thus suggesting the importance of the C3 region as a binding site. Purified gC from HSV-1, but not HSV-2, inhibited the binding of factor H and properdin but not of CR1 to C3b. The binding of iC3b to CR2, a molecule involved in B-cell activation and binding of the Epstein-Barr virus, was also inhibited by the HSV-1 protein. As factor H and properdin, the binding of which was inhibited by gC, are important regulators of the alternative complement pathway, these data further support a role of gC in the evasion of HSV from a major first-line host defence mechanism, i.e. the complement system. In addition, the inhibition of the C3/CR2 interaction may suggest a possible immunoregulatory role of HSV glycoprotein C.
单纯疱疹病毒（HSV）编码一种蛋白，即糖蛋白C（gC），它可与补体第三成分结合，补体第三成分是补体激活的中心介质。在本研究中，对1型单纯疱疹病毒（HSV-1）的gC与已知的人类补体调节蛋白H因子、备解素、B因子、补体受体1（CR1）和2（CR2）之间的结构和功能关系进行了研究。使用纯化的补体成分、合成肽、针对不同C3片段的抗血清以及对C3配体相互作用具有已知抑制作用的抗C3单克隆抗体（mAb），研究了gC与C3b的相互作用。所有以不同方式抑制gC/C3b相互作用的mAb，也可阻止C3片段与H因子、B因子、CR1或CR2的结合。用代表不同C3区域的合成肽或B因子和C3d未观察到阻断作用，而C3b、C3c和H因子具有抑制作用，纯化的gC也具有抑制作用。gC与眼镜蛇毒因子（CVF）无结合，CVF是一种源自眼镜蛇腺体的C3c样片段。纯化的gC可与iC3、iC3b和C3c结合，但不能与C3d结合。糖蛋白C仅与源自牛和猪血浆的iC3弱结合，因此表明该病毒蛋白对合适宿主具有偏好性。还观察到gC与经蛋白酶水解的C3片段结合，尤其是与β链结合，因此表明C3区域作为结合位点的重要性。来自HSV-1而非HSV-2的纯化gC可抑制H因子和备解素与C3b的结合，但不能抑制CR1与C3b的结合。HSV-1蛋白也可抑制iC3b与CR2的结合，CR2是一种参与B细胞活化和爱泼斯坦-巴尔病毒结合的分子。由于其结合被gC抑制的H因子和备解素是替代补体途径的重要调节因子，这些数据进一步支持gC在HSV逃避主要的一线宿主防御机制即补体系统中发挥作用。此外，对C3/CR2相互作用的抑制可能提示HSV糖蛋白C具有可能的免疫调节作用。
