INTERACTION OF SV40 WITH MHC CLASS 1 PROTEINS

我们提供了三条证据，这三条证据共同有力地暗示， 1类蛋白是SV 40的特异性细胞表面受体：1）SV 40 特异性和竞争性抑制抗-MHC 1单克隆抗体与 细胞表面; 2）用抗-MHC 1单克隆抗体阻断物预处理细胞 SV 40感染;和3）暴露于MHC 1类-人淋巴母细胞 细胞与SV 40病毒粒子的结合不产生产生病毒T抗原的细胞 而用SV 40 DNA转染则可以。 为了使案件引人注目，我们 在此建议还显示以下内容：1）插入和 - 将用于MHC 1类表达的基因表达为MHC 1类， 细胞使它们容易受到SV 40的感染; 2）SV 40和MHC 1类蛋白可以从细胞表面共免疫沉淀;和3） 与纯化的可溶性MHC 1类蛋白孵育抑制SV 40， 传染性 我们将应用相同的标准来确定MHC是否 1类蛋白也作为相关多瘤病毒的受体 JCV和BKV。 我们将考虑一些可能的后果，MHC 1类蛋白服务 SV 40受体。 我们将确定是否积累 细胞表面的子代SV 40病毒粒子（我们的观察）可能抑制 MHC限制性CTL介导的细胞杀伤。 我们还将确定 最近报道的SV 40对顶膜结构域的偏好， 极化的上皮细胞也与类似的不对称性相关， 1类MHC蛋白的分布。 最后，据报告， SV 40优先从极化细胞的顶端表面释放。 我们建议确定SV 40的靶向释放是否可能涉及， 依赖于其与细胞内MHC 1类蛋白的相互作用。

We offer three lines of evidence which together strongly imply that MHC class 1 proteins are the specific cell surface receptor of SV40: 1) SV40 specifically and competitively inhibits the binding of an anti-MHC 1 mAB to the cell surface; 2) pretreatment of cells with the anti-MHC 1 mAB blocks infection by SV40; and 3) exposure of MHC class 1- human lymphoblastoid cells to SV40 virions does not yield viral T antigen-producing cells whereas transfection with SV40 DNA does. To make the case compelling, we propose here to also show the following: 1) that the insertion and expression of the gene for MHC class 1 expression into the MHC class 1- cells renders them susceptible to infection by SV40; 2) that SV40 and MHC class 1 proteins can be co-immunoprecipitated from the cell surface; and 3) that incubation with purified soluble MHC class 1 protein inhibits SV40 infectivity. We will apply the same criteria to determine whether MHC class 1 proteins also serve as the receptor of the related polyomaviruses of humans, JCV and BKV. We will consider some possible consequences of MHC class 1 proteins serving as the SV40 receptor. We will determine whether the accumulation of progeny SV40 virions at the cell surface (our observation) might inhibit MHC-restricted CTL-mediated cell killing. We will also determine whether the recently reported preference of SV40 for the apical membrane domain of polarized epithelial cells correlates with a similar asymmetry in the distribution of class 1 MHC proteins. Finally, it was also reported that SV40 is preferentially released from the apical surface of polarized cells. We propose to determine if the targeted release of SV40 might involve, and be dependent upon, its interaction with intracellular MHC class 1 proteins.