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了MHC 1类蛋白是SV40的特异性细胞表面受体 特异性和竞争性地抑制抗MHC 1单抗与 细胞表面；2)用抗MHC-1单抗对细胞进行预处理 SV40感染；以及3)暴露于MHC-1类人淋巴母细胞 细胞对SV40病毒粒子不产生病毒T抗原产生细胞 而用SV40DNA转染组则相反。为了使案件更具说服力，我们 在此建议还显示以下内容：1)插入和 MHC-1类基因在MHC-1中的表达 细胞使它们容易感染SV40；2)SV40和MHC 1类蛋白可以从细胞表面免疫共沉淀；以及3) 与纯化的可溶性MHC-1蛋白孵育可抑制SV40 传染性。我们将应用相同的标准来确定MHC是否 1类蛋白也是相关多瘤病毒的受体。 人类、JCV和BKV。 我们将考虑MHC 1类蛋白服务的一些可能后果 作为SV40受体。我们将确定是否积累了 子代SV40病毒粒子在细胞表面(我们的观察)可能抑制 MHC限制性CTL介导的细胞杀伤。我们还将确定是否 新近报道的SV40对根尖膜结构域的偏好 极化的上皮细胞与类似的不对称性相关 1类MHC蛋白的分布。最后，据报道， SV40优先从极化细胞的顶面释放。 我们建议确定SV40的定向发布是否可能涉及 依赖于它与细胞内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.