Schnorr J J, Dunster L M, Nanan R, Schneider-Schaulies J, Schneider-Schaulies S, ter Meulen V
Institut für Virologie und Immunobiologie, Universität Würzburg, Germany.
Eur J Immunol. 1995 Apr;25(4):976-84. doi: 10.1002/eji.1830250418.
CD46, the major component of the measles virus (MV) receptor complex and a member of the regulators of complement activity (RCA) gene cluster, is down-regulated in MV-infected cells. We investigated whether the reduction of surface CD46 correlates with enhanced sensitivity of lymphoid and monocytic cells to lysis by activated complement. On human U937 cells, acutely or persistently infected with MV-Edmonston (ED) vaccine strain, infection-dependent down-regulation of CD46 confers sensitivity to activated complement, regardless of the pathway of activation and the specificity of the activating antibodies. Interestingly, down-regulation of CD46 alone is sufficient to confer susceptibility of cells to complement lysis despite the continued surface expression of other RCA proteins such as CD35 and CD55. In primary cultures, both peripheral blood lymphocytes and macrophages are efficiently lysed in the presence of complement activated via the alternative pathway after MV infection. In contrast to the MV-ED infection, infection of cells with the lymphotropic MV wild-type strain WTF does not down-regulate CD46. Cells infected with MV-WTF do not exhibit enhanced susceptibility to complement lysis. These data suggest that MV strains similar to WTF that do not down-regulate CD46 may have an enhanced potential for replication and dissemination within the human host, whereas complement-mediated elimination of cells infected with CD46-down-regulating strains of MV, such as ED, may limit the spread of MV infection, and could thus represent an attenuating factor for MV.
CD46是麻疹病毒（MV）受体复合物的主要成分，也是补体活性调节因子（RCA）基因簇的成员之一，在MV感染的细胞中表达下调。我们研究了表面CD46的减少是否与淋巴细胞和单核细胞对活化补体裂解的敏感性增强相关。在人U937细胞中，急性或持续感染MV-埃德蒙斯顿（ED）疫苗株，CD46的感染依赖性下调赋予细胞对活化补体的敏感性，无论活化途径和活化抗体的特异性如何。有趣的是，尽管其他RCA蛋白如CD35和CD55持续在表面表达，但单独的CD46下调就足以使细胞对补体裂解敏感。在原代培养中，MV感染后，外周血淋巴细胞和巨噬细胞在通过替代途径活化的补体存在下均被有效裂解。与MV-ED感染相反，用嗜淋巴细胞性MV野生型毒株WTF感染细胞不会下调CD46。感染MV-WTF的细胞对补体裂解的敏感性没有增强。这些数据表明，与WTF相似的不下调CD46的MV毒株在人类宿主内可能具有增强的复制和传播潜力，而补体介导的清除感染下调CD46的MV毒株（如ED）的细胞可能会限制MV感染的传播，因此可能是MV的一个减毒因素。
