Altered expression of host-encoded complement regulators on human cytomegalovirus-infected cells
Altered expression of host-encoded complement regulators on human cytomegalovirus-infected cells
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DOI：
10.1002/eji.1830260719
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发表时间：
1996-07-01
影响因子：
5.4
通讯作者：
Devine, DV
中科院分区：
文献类型：
--
作者：
Spiller, OB;Morgan, BP;Devine, DV
人巨细胞病毒（HCMV）感染的细胞在抗HCMV抗体存在下持续存在，表明HCMV已进化出逃避宿主免疫防御的机制。由于没有病毒编码的补体抑制剂已被确定为HCMV，我们假设，HCMV感染可能会改变宿主编码的细胞表面补体抑制剂的表达。在此，我们报告，细胞表面表达的两个补体调节蛋白，CD 55和CD 46，这是补体激活（RCA）基因簇的调节器的成员，增加了8倍后，感染成纤维细胞或胶质母细胞瘤细胞与HCMV，但不是感染HSV-1或腺病毒。然而，细胞表面表达的第三补体调节，CD 59，这不是一个成员的RCA基因簇，在HCMV感染期间没有改变。使用纯化的补体成分的功能研究表明，上调CD 55抑制了HCMV感染细胞上的细胞相关C3转化酶的活性。此外，增加的CD 55表达保护受感染的细胞免受补体介导的裂解，这种作用与HCMV感染的时间直接相关。宿主编码的补体调节蛋白的表达增加可以通过增加感染细胞对补体介导的裂解的抗性和减少C3衍生产物在细胞表面上的沉积来保护HCMV感染细胞免受体内宿主免疫应答。
Human cytomegalovirus (HCMV)-infected cells persist in the presence of anti-HCMV antibody, suggesting that HCMV has evolved mechanisms to evade host immune defenses. Insofar as no virus-encoded complement inhibitors have been identified for HCMV, we hypothesized that HCMV infection may alter the expression of host-encoded cell surface complement inhibitors. Herein, we report that cell surface expression of two complement regulator proteins, CD55 and CD46, which are members of the regulators of complement activation (RCA) gene cluster, increased up to eightfold following infection of fibroblasts or glioblastoma cells with HCMV, but not after infection with HSV-1 or adenovirus. However, the cell surface expression of a third complement regulator, CD59, which is not a member of the RCA gene cluster, was not altered during HCMV infection. Functional studies using purified complement components demonstrated that up-regulation of CD55 suppressed the activity of cell-associated C3 convertases on HCMV-infected cells. Furthermore, increased CD55 expression protected infected cells from complement-mediated lysis, an effect which directly correlated with the length of HCMV infection. Increased expression of host-encoded complement regulator proteins may provide protection of HCMV-infected cells from the host immune response in vivo, through increasing the resistance of infected cells to complement-mediated lysis and decreasing the deposition of C3-derived products on the cell surface.