Cellular and species resistance to murine amphotropic, gibbon ape, and feline subgroup C leukemia viruses is strongly influenced by receptor expression levels and by receptor masking mechanisms.
Cellular and species resistance to murine amphotropic, gibbon ape, and feline subgroup C leukemia viruses is strongly influenced by receptor expression levels and by receptor masking mechanisms.
复制标题
细胞和物种对鼠类双嗜性、长臂猿和猫科C亚组白血病病毒的抗性受到受体表达水平和受体掩蔽机制的强烈影响。
DOI：
10.1128/jvi.74.20.9797-9801.2000
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发表时间：
2000
影响因子：
5.4
通讯作者：
Kabat,D
中科院分区：
文献类型：
--
作者：
Tailor,CS;Nouri,A;Kabat,D
中国仓鼠卵巢（CHO）细胞对巨猿白血病病毒（GALV）和嗜中性鼠白血病病毒（A-MLV）的感染具有抗性，除非用衣霉素（一种N-连接糖基化抑制剂）预处理。这些病毒使用相关的钠磷酸同向转运蛋白Pit 1和Pit 2，分别作为非仓鼠细胞中的受体，有证据表明，CHO细胞的相应转运蛋白可能被衣霉素敏感的分泌抑制剂所掩盖。尽管据报道E36系中国仓鼠细胞分泌推定的Pit 2抑制剂，并对抑制性CHO因子敏感，但在不存在衣霉素的情况下，E36细胞对GALV和A-MLV高度敏感。此外，E36 Pit 2在CHO细胞中的表达赋予两种病毒衣霉素独立的亲和性。基于后一结果，表明E36 Pit 2必须在功能上不同于CHO细胞的内源Pit 2。为了验证这些想法，我们分析了CHO细胞中CHO Pit 1和Pit 2的受体特性。令人惊讶且违反直觉的是，CHO Pit 2表达载体转染到CHO细胞中赋予对GALV和A-MLV的强易感性，并且CHO Pit 1的类似过表达赋予对GALV的易感性。因此，CHO Pit 2是两种病毒的混杂功能性受体，而CHO Pit 1是GALV的功能性受体。类似地，我们发现，小鼠成纤维细胞对C亚群猫白血病病毒（FeLV-C）的天然抗性仅通过内源性FeLV-C受体同源物的过表达而消除。这些结果证明了一种新的和简单的方法，揭露潜伏的逆转录病毒受体的活动，发生在一些细胞。具体地，由亚阈值水平的受体表达或由化学计量限制的掩蔽或干扰机制引起的对逆转录病毒的抗性可以简单地通过在相同细胞中过表达内源性受体来有效地克服。
Chinese hamster ovary (CHO) cells are resistant to infections by gibbon ape leukemia virus (GALV) and amphotropic murine leukemia virus (A-MLV) unless they are pretreated with tunicamycin, an inhibitor of N-linked glycosylation. These viruses use the related sodium-phosphate symporters Pit1 and Pit2, respectively, as receptors in nonhamster cells, and evidence has suggested that the corresponding transporters of CHO cells may be masked by tunicamycin-sensitive secreted inhibitors. Although the E36 line of Chinese hamster cells was reported to secrete the putative Pit2 inhibitor and to be sensitive to the inhibitory CHO factors, E36 cells are highly susceptible to both GALV and A-MLV in the absence of tunicamycin. Moreover, expression of E36 Pit2 in CHO cells conferred tunicamycin-independent susceptibilities to both viruses. Based on the latter results, it was suggested that E36 Pit2 must functionally differ from the endogenous Pit2 of CHO cells. To test these ideas, we analyzed the receptor properties of CHO Pit1 and Pit2 in CHO cells. Surprisingly, and counterintuitively, transfection of a CHO Pit2 expression vector into CHO cells conferred strong susceptibility to both GALV and A-MLV, and similar overexpression of CHO Pit1 conferred susceptibility to GALV. Thus, CHO Pit2 is a promiscuous functional receptor for both viruses, and CHO Pit1 is a functional receptor for GALV. Similarly, we found that the natural resistance ofMus dunnitail fibroblasts to subgroup C feline leukemia viruses (FeLV-C) was eliminated simply by overexpression of the endogenous FeLV-C receptor homologue. These results demonstrate a novel and simple method to unmask latent retroviral receptor activities that occur in some cells. Specifically, resistances to retroviruses that are caused by subthreshold levels of receptor expression or by stoichiometrically limited masking or interference mechanisms can be efficiently overcome simply by overexpressing the endogenous receptors in the same cells.