The N-terminal region of the murine coronavirus spike glycoprotein is associated with the extended host range of viruses from persistently infected murine cells
The N-terminal region of the murine coronavirus spike glycoprotein is associated with the extended host range of viruses from persistently infected murine cells
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DOI：
10.1128/jvi.78.17.9073-9083.2004
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发表时间：
2004-09-01
影响因子：
5.4
通讯作者：
Holmes, KV
中科院分区：
文献类型：
--
作者：
Schickli, JH;Thackray, LB;Holmes, KV
虽然小鼠冠状病毒自然只感染小鼠，但从持续感染的小鼠细胞培养物中衍生的几种病毒变体具有更广泛的宿主范围。小鼠肝炎病毒（MHV）变异MHV/ BHK可以感染仓鼠、大鼠、猫、狗、猴和人类细胞系，但不感染猪睾丸（ST）猪细胞系（J. H. Schickli， B. D. Zelus， D. E. Wentworth， S. G. Sawicki， K. V. Holmes， J.病毒学报，71:9499- 9507,1997）。与亲本MHV株A59相比，MHV/BHK刺突(S)基因有63个点突变，一个21-by的插入物编码了56个氨基酸替换和一个7个氨基酸插入物。在仓鼠细胞中筛选MHV- a59和MHV/BHK之间的重组病毒。所有重组体在MHV/BHK的n端区域都保留了21个氨基酸取代和一个7个氨基酸插入，表明这些残基与MHV/BHK的宿主范围扩大有关。流式细胞术显示MHV-A59仅与表达小鼠糖蛋白受体CEACAM1a的细胞结合。相比之下，MHV/BHK和重组病毒k6c与仓鼠（BHK）和ST细胞以及小鼠细胞结合，其中21个氨基酸取代和7个氨基酸插入S。因此，在MHV/BHK的S糖蛋白n端区域，21个氨基酸的替换和7个氨基酸的插入赋予了结合并在某些情况下感染非小鼠物种细胞的能力。
Although murine coronaviruses naturally infect only mice, several virus variants derived from persistently infected murine cell cultures have an extended host range. The mouse hepatitis virus (MHV) variant MHV/ BHK can infect hamster, rat, cat, dog, monkey, and human cell lines but not the swine testis (ST) porcine cell line (J. H. Schickli, B. D. Zelus, D. E. Wentworth, S. G. Sawicki, and K. V. Holmes, J. Virol. 71:9499-9507, 1997). The spike (S) gene of MHV/BHK had 63 point mutations and a 21-by insert that encoded 56 amino acid substitutions and a 7-amino-acid insert compared to the parental MHV strain A59. Recombinant viruses between MHV-A59 and MHV/BHK were selected in hamster cells. All of the recombinants retained 21 amino acid substitutions and a 7-amino-acid insert found in the N-terminal region of S of MHV/BHK, suggesting that these residues were responsible for the extended host range of MHV/BHK. Flow cytometry showed that MHV-A59 bound only to cells that expressed the murine glycoprotein receptor CEACAM1a. In contrast, MHV/BHK and a recombinant virus, k6c, with the 21 amino acid substitutions and 7-amino-acid insert in S bound to hamster (BHK) and ST cells as well as murine cells. Thus, 21 amino acid substitutions and a 7-amino-acid insert in the N-terminal region of the S glycoprotein of MHV/BHK confer the ability to bind and in some cases infect cells of nonmurine species.