Acta Virol. 2020;64(4):433-450. doi: 10.4149/av_2020_406.
The mechanisms of rotavirus entry into the target cell are described as a multi-step event in which the virions are bound to sialic acid (SA), followed by interaction with heat shock cognate protein 70 (Hsc70), some integrins and protein disulfide isomerase (PDI). However, the cell surface receptor molecules facilitating the entry of tumor cell-adapted rotavirus are not completely characterized. Using infection blocking assays with antibodies to some heat shock proteins (HSPs) and also some inhibitors of these cellular proteins, we were able to identify the cell surface Hsp90, Hsp70, Hsc70, Hsp60, Hsp40, PDI and integrin β3 as receptors of tumor cell-adapted rotavirus in Reh cells. Furthermore, the results also indicated that these rotavirus receptors are associated with lipid microdomains (rafts). Our findings provide evidence that rotavirus tropism for these human acute lymphocytic leukemia cells is explained by the relatively high expression of some HSPs in rafts. The results shown here encourage further research aim at evaluating the potential use of rotaviruses as an oncolytic agent for the treatment of some cancers. Keywords: heat shock proteins; rotavirus; cell receptor; cancer; oncolytic virus.
轮状病毒进入靶细胞的机制被描述为一个多步骤事件,其中病毒与唾液酸(SA)结合,然后与热休克同源蛋白 70(Hsc70)、一些整合素和蛋白二硫键异构酶(PDI)相互作用。然而,促进肿瘤细胞适应的轮状病毒进入的细胞表面受体分子尚未完全表征。我们使用针对一些热休克蛋白(HSPs)的抗体和这些细胞蛋白的一些抑制剂的感染阻断测定,能够鉴定出 Reh 细胞中肿瘤细胞适应的轮状病毒的细胞表面 HSP90、HSP70、Hsc70、HSP60、HSP40、PDI 和整合素 β3 作为受体。此外,结果还表明这些轮状病毒受体与脂质微区(筏)有关。我们的研究结果表明,轮状病毒对这些人类急性淋巴细胞白血病细胞的嗜性是由筏中某些 HSPs 的相对高表达所解释的。这里显示的结果鼓励进一步研究评估轮状病毒作为治疗某些癌症的溶瘤剂的潜在用途。关键词:热休克蛋白;轮状病毒;细胞受体;癌症;溶瘤病毒。