Gerlier D, Loveland B, Varior-Krishnan G, Thorley B, McKenzie I F, Rabourdin-Combe C
Immunobiologie Moléculaire, CNRS-ENS UMR 49, Lyon, France.
J Gen Virol. 1994 Sep;75 ( Pt 9):2163-71. doi: 10.1099/0022-1317-75-9-2163.
Human CD46, a member of the family of regulators of complement activation, has been shown recently to act as a measles virus (MV) receptor, interacting with the virus envelope glycoprotein haemagglutinin (HA). Owing to alternative RNA splicing, several CD46 isoforms are co-expressed in all tissues except erythrocytes. The optional exons encode extracellular serine-, threonine- and proline-rich regions of CD46 (designated STP-A, -B and -C) which are located proximal to the plasma membrane, and alternatively cytoplasmic tails (CYT1 or CYT2). The ability of the BC-CYT2, B-CYT2 and BC-CYT1 CD46 isoforms, expressed in rodent Chinese hamster ovary (CHO) cells, to mediate MV infection was tested. Every isoform was recognized by a monoclonal antibody (MAb), MCI20.6, which recognizes the MV-binding site on CD46. CHO cells expressing any of these CD46 isoforms were able to bind MV, the level of binding correlating with the CD46 expression level. Likewise, MV infection induced the cell-cell fusion of all CD46-expressing CHO cells but not of the parental CHO cells. Accordingly, MV replication was observed after infection of CHO cells expressing each CD46 isoform but not after infection of parental CHO cells. Finally, cell surface expression of every isoform was decreased after infection by MV. Altogether these data showed that the specific STP regions of CD46 played no major role in HA-mediated MV binding to CD46, virus infection and virus-induced down-regulation of CD46. Moreover, the CYT1 and CYT2 cytoplasmic tails of CD46 are either functionally similar although having distinct amino acid sequences or are dispensable for interaction with HA of MV.
人CD46是补体激活调节因子家族的一员，最近已被证明可作为麻疹病毒（MV）受体，与病毒包膜糖蛋白血凝素（HA）相互作用。由于RNA可变剪接，除红细胞外，几种CD46亚型在所有组织中共同表达。选择性外显子编码位于质膜近端的CD46富含细胞外丝氨酸、苏氨酸和脯氨酸的区域（分别命名为STP-A、-B和-C），以及可变的胞质尾（CYT1或CYT2）。测试了在啮齿类中国仓鼠卵巢（CHO）细胞中表达的BC-CYT2、B-CYT2和BC-CYT1 CD46亚型介导MV感染的能力。每种亚型都能被单克隆抗体（MAb）MCI20.6识别，该抗体识别CD46上的MV结合位点。表达这些CD46亚型中任何一种的CHO细胞都能够结合MV，结合水平与CD46表达水平相关。同样，MV感染诱导了所有表达CD46的CHO细胞的细胞间融合，但未诱导亲本CHO细胞的融合。因此，在用每种CD46亚型感染CHO细胞后观察到MV复制，但在用亲本CHO细胞感染后未观察到。最后，MV感染后每种亚型的细胞表面表达均降低。这些数据表明，CD46的特定STP区域在HA介导的MV与CD46结合、病毒感染以及病毒诱导的CD46下调中不起主要作用。此外，CD46的CYT1和CYT2胞质尾虽然氨基酸序列不同，但功能相似，或者对于与MV的HA相互作用是可有可无的。
