Removal of either N-glycan site from the envelope receptor binding domain of Moloney and Friend but not AKV mouse ecotropic gammaretroviruses alters receptor usage.

Removal of either N-glycan site from the envelope receptor binding domain of Moloney and Friend but not AKV mouse ecotropic gammaretroviruses alters receptor usage.
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DOI:
10.1016/j.virol.2009.06.015
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发表时间:
2009-09-01
期刊:
影响因子:
3.7
通讯作者:
Kozak, Christine A.
Kozak, Christine A.
中科院分区:
医学3区
文献类型:
--
作者:
Knoper, Ryan C.;Ferrarone, John;Yan, Yuhe;Lafont, Bernard A. R.;Kozak, Christine A.

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从Friend、Moloney和AKV小鼠生态型伽马逆转录病毒的包膜糖蛋白中去掉了三个N连接的糖基化位点:受体结合区域的GS1和GS2;以及与结合后细胞融合有关的区域GS8。检测了突变体感染表达4种CAT-1受体变异体的啮齿动物细胞的能力。三个突变体(Mo-GS1、Mo-GS2、Fr-GS1)可感染NIH3T3和大鼠XC细胞,但在M.Dunni细胞和对生态亲和性病毒敏感的中国仓鼠细胞系Lec8中受到严重限制。这种限制在表达M.Dunni dCAT-1的雪貂细胞中复制,但不在表达NIH 3T3 MCAT-1的细胞中复制。病毒结合分析、假型分析和糖基化抑制剂的使用进一步表明,限制主要是由于受体的多态,以及在邓尼分枝杆菌细胞中,与细胞蛋白的糖基化有关。病毒被膜多糖的大小或类型不影响传染性。因此,由于N-糖链缺失引起的宿主范围的变化是受体特异性的、细胞特异性的、病毒类型特异性的和糖链位点特异性的。
Three N-linked glycosylation sites were removed from the envelope glycoproteins of Friend, Moloney, and AKV mouse ecotropic gammaretroviruses: gs1 and gs2, in the receptor binding domain; and gs8, in a region implicated in post-binding cell fusion. Mutants were tested for their ability to infect rodent cells expressing 4 CAT-1 receptor variants. Three mutants (Mo-gs1, Mo-gs2, Fr-gs1) infect NIH 3T3 and rat XC cells, but are severely restricted in M. dunni cells and Lec8, a Chinese hamster cell line susceptible to ecotropic virus. This restriction is reproduced in ferret cells expressing M. dunni dCAT-1, but not in cells expressing NIH 3T3 mCAT-1. Virus binding assays, pseudotype assays, and use of glycosylation inhibitors further suggest that restriction is primarily due to receptor polymorphism and, in M. dunni cells, to glycosylation of cellular proteins. Virus envelope glycan size or type does not affect infectivity. Thus, host range variation due to N-glycan deletion is receptor variant-specific, cell specific, virus type-specific, and glycan site-specific.
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