SINGLE AMINO-ACID SUBSTITUTIONS IN GD OF HERPES-SIMPLEX VIRUS-1 CONFER RESISTANCE TO GD-MEDIATED INTERFERENCE AND CAUSE CELL-TYPE-DEPENDENT ALTERATIONS IN INFECTIVITY

SINGLE AMINO-ACID SUBSTITUTIONS IN GD OF HERPES-SIMPLEX VIRUS-1 CONFER RESISTANCE TO GD-MEDIATED INTERFERENCE AND CAUSE CELL-TYPE-DEPENDENT ALTERATIONS IN INFECTIVITY
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DOI：
10.1006/viro.1994.1098
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发表时间：
1994-02-15
期刊：
VIROLOGY
影响因子：
3.7
通讯作者：
SPEAR, PG
SPEAR, PG
中科院分区：
医学3区
文献类型：
--
作者：
DEAN, HJ;TERHUNE, SS;SPEAR, PG

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被引文献

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先前的研究表明，细胞相关单纯疱疹病毒(HSV)糖蛋白gD可以干扰HSV和其他甲型疱疹病毒对细胞的感染，并且可以分离出抵抗这种gD介导的干扰的HSV突变体。在这里，我们报告了被选来抵抗gD介导的干扰的HSV突变体对不表达gD的细胞的特定感染性发生了改变。与野生型亲本株相比，两个独立衍生的突变体感染Hep-2细胞的能力减弱，感染中国仓鼠卵巢细胞的能力增强。突变体在与细胞结合的能力上与亲本菌株没有显著差异，但在结合后的感染步骤上有所不同，可能是渗透。这两个突变体在GD中具有不同的氨基酸替换(Q27P和Q27R)。标记转移实验表明，这些氨基酸的替换导致了对Gd介导的干扰的抗性以及侵染性的改变。因此，gD结构的微小变化不仅可以增强对gD介导的干扰的抵抗力，还可以改变HSV穿透不同细胞类型的相对效率。
Previous studies have shown that cell-associated herpes simplex virus (HSV) glycoprotein gD can interfere with infection of the cells by HSV and other alphaherpesviruses and that HSV mutants resistant to this gD-mediated interference can be isolated. Here we report that HSV mutants selected for resistance to gD-mediated interference are altered in specific infectivity for cells that do not express gD. Two independently derived mutants were shown to be impaired in ability to infect HEp-2 cells and enhanced in ability to infect Chinese hamster ovary cells, compared with the wild-type parental strain. The mutants were not significantly different from the parental strain in ability to bind to cells but differed in a postbinding step required for infectivity, probably penetration. The two mutants were shown to have different amino acid substitutions (Q27P and Q27R) in gD. Marker transfer experiments demonstrated that the resistance to gD-mediated interference as well as the altered infectivities resulted from these amino acid substitutions. Thus, small changes in gD structure can not only confer resistance to gD-mediated interference but also alter the relative efficiencies with which HSV penetrates into different cell types.