Analysis of the unique hamster cell tropism of ecotropic murine leukemia virus PVC-211
Analysis of the unique hamster cell tropism of ecotropic murine leukemia virus PVC-211
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DOI：
10.1128/jvi.70.12.8534-8539.1996
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发表时间：
1996-12-01
影响因子：
5.4
通讯作者：
Ruscetti, SK
中科院分区：
文献类型：
--
作者：
Masuda, M;Masuda, M;Ruscetti, SK
PVC-211小鼠白血病病毒（MuLV）是Friend MuLV（F-MuLV）的一种神经致病性变体。我们实验室以前的研究表明，与亲本F-MuLV不同，PVC-211 MuLV可以有效感染大鼠脑毛细血管内皮细胞，并且它已经获得了导致其扩大细胞向性的遗传变化。为了确定PVC-211 MuLV是否也扩大了其宿主范围，我们测试了其对中国仓鼠卵巢来源的CHO-K1细胞的感染性，该细胞通常对亲嗜性MuLV具有抗性。结果表明，PVC-211 MuLV而不是F-MuLV对CHO-K1细胞具有高度感染性。使用CHO-K1细胞的糖基化抑制剂和糖基化突变体的研究以及干扰研究表明，PVC-211 MuLV已获得与CHO-K1细胞上的亲嗜性MuLV受体相互作用的能力，该受体已经历糖基化依赖性修饰。使用PVC-211 MuLV和F-MuLV之间的嵌合病毒，我们能够在PVC-211 MuLV的env基因内定位对CHO-K1细胞嗜性至关重要的病毒遗传元件，并表明包膜糖蛋白SU的116位甘氨酸和129位赖氨酸是重要的。这些病毒决定簇似乎也赋予了对普通亲嗜性MuLV具有抗性的其他仓鼠细胞嗜性。进一步研究PVC-211 MuLV与仓鼠细胞上的受体之间的相互作用可能为受体识别和结合bg病毒包膜糖蛋白的分子机制提供新的见解。
PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV (F-MuLV). Previous studies from our laboratory demonstrated that unlike the parental F-MuLV, PVC-211 MuLV can infect rat brain capillary endothelial cells efficiently and that it has acquired genetic changes responsible for its expanded cellular tropism. To determine if PVC-211 MuLV also has expanded its host range, we tested its infectivity on Chinese hamster ovary-derived CHO-k1 cells, which are generally resistant to ecotropic MuLV, The results indicated that PVC-211 MuLV, but not F-MuLV, mas highly infectious for CHO-K1 cells. Studies using glycosylation inhibitors and glycosylation mutants of CHO-K1 cells, as well as interference studies, suggested that PVC-211 MuLV has acquired the ability to interact with the ecotropic MuLV receptor on CHO-K1 cells that has undergone glycosylation-dependent modification. Using chimeric viruses between PVC-211 MuLV and F-MuLV, we were able to localize the viral genetic element crucial for CHO-K1 cell tropism within the env gene of PVC-211 MuLV and show that glycine at position 116 and lysine at position 129 of the envelope glycoprotein SU were important. These viral determinants also appear to confer tropism for other hamster cells resistant to ordinary ecotropic MuLVs. Further studies on the interaction between PVC-211 MuLV and the receptor on hamster cells may provide novel insights into the molecular mechanisms for receptor recognition and binding bg viral envelope glycoproteins.