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SAT1 型口蹄疫病毒衣壳蛋白分析:受体使用对病毒粒子特性的影响。

Analysis of SAT1 type foot-and-mouth disease virus capsid proteins: influence of receptor usage on the properties of virus particles.

机构信息

Transboundary Animal Diseases Programme, Onderstepoort Veterinary Institute, Agricultural Research Council, Old Soutpan Road, Onderstepoort, Pretoria 0110, South Africa.

出版信息

Virus Res. 2011 Feb;155(2):462-72. doi: 10.1016/j.virusres.2010.12.002. Epub 2010 Dec 15.

DOI:10.1016/j.virusres.2010.12.002
PMID:21167231
Abstract

The three SAT serotype viruses, endemic in Africa, are well known for their difficulty to adapt to cell culture. The viral mechanism involved in foot-and-mouth disease virus (FMDV) tissue tropism and cell-entry is not well understood. A recombinant, small plaque-forming virus (vSAT1tc), derived from a tissue culture-adapted SAT1 virus (SAR/9/81tc), revealed four amino acid substitutions (VP3 Asp192→Tyr; VP3 Ser217→Ile; VP1 Ala69→Gly and VP1 Asn110→Lys) in the capsid, compared to the SAR/9/81wt isolate collected from infected impala epithelium. One substitution added a positively charged lysine residue to the short βF-βG loop of VP1. Furthermore, vSAT1tc displayed a high affinity for CHO-K1 cells possibly via interaction with negatively charged sulphated polysaccharides while SAT1 impala strain relied strongly on α(V)β6 integrin receptors for cell entry. The cell culture adaptation and small plaque phenotype of vSAT1tc was accompanied by differences in particle aggregation and significant differences in acid stability. Based on limited cross neutralization data, the antigenic features seem to be unchanged. Thus, acquisition of positively charged residues in the virion may be beneficial for adaptation of SAT type field strains to cell culture.

摘要

三种 SAT 血清型病毒在非洲流行,它们难以适应细胞培养是众所周知的。口蹄疫病毒(FMDV)组织嗜性和细胞进入的病毒机制尚未得到很好的理解。一种源自组织培养适应的 SAT1 病毒(SAR/9/81tc)的重组小噬菌斑形成病毒(vSAT1tc),与从受感染的大羚羊上皮组织中收集的 SAR/9/81wt 分离株相比,在衣壳中显示出四个氨基酸取代(VP3 Asp192→Tyr;VP3 Ser217→Ile;VP1 Ala69→Gly 和 VP1 Asn110→Lys)。一个取代在 VP1 的短βF-βG 环中添加了一个带正电荷的赖氨酸残基。此外,vSAT1tc 对 CHO-K1 细胞具有高亲和力,可能是通过与带负电荷的硫酸多糖相互作用,而 SAT1 大羚羊株则强烈依赖α(V)β6 整合素受体进入细胞。vSAT1tc 的细胞培养适应和小噬菌斑表型伴随着颗粒聚集的差异和酸稳定性的显著差异。基于有限的交叉中和数据,抗原特征似乎没有改变。因此,病毒粒子中带正电荷的残基的获得可能有利于 SAT 型田间株适应细胞培养。

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