Evolution subverting essentiality: Dispensability of the cell attachment Arg-Gly-Asp motif in multiply passaged foot-and-mouth disease virus
Evolution subverting essentiality: Dispensability of the cell attachment Arg-Gly-Asp motif in multiply passaged foot-and-mouth disease virus
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DOI：
10.1073/pnas.94.13.6798
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发表时间：
1997-06-24
影响因子：
11.1
通讯作者：
Domingo, E
中科院分区：
文献类型：
--
作者：
Martinez, MA;Verdaguer, N;Domingo, E
口蹄疫病毒利用保守的Arg-Gly-Asp三联体附着于软管细胞，并且该基序被认为是病毒存活所必需的，我们报道了该三联体-其也是参与细胞与细胞粘附的广泛基序-可以在携带它的病毒的短期进化后变得不稳定。显示了对中和单克隆抗体具有抗性的抗原变体的改变的库。改变的库包括在Arg-Gly-Asp基序处具有取代的变体，缺乏该序列的突变体在细胞培养物中正常复制并且与亲本病毒无法区分。对单个FMDV克隆的研究表明，位于含有Arg-Gly-Asp三联体mag的环周围的衣壳表面上的氨基酸替换介导了该基序的可分配性。结果表明，在恒定的生物环境中进化的口蹄疫病毒准种具有使RNA病毒的RNA受体识别基序完全保持不变的能力，并为病毒的正常复制提供了另一条途径。因此，高度保守的基序的变异性，甚至是病毒从功能性细胞基序进化而来的基序的变异性，都可能导致RNA病毒在自然界中的表型灵活性。
Aphthoviruses use a conserved Arg-Gly-Asp triplet for attachment to hose cells and this motif is believed to be essential for virus viability, Were we report that this triplet-which is also a widespread motif involved in cell-to-cell adhesion-can become dispensable upon short-term evolution of the virus harboring it. Foot-and-mouth disease virus (FMDV), which was multiply passaged in cell culture, showed an altered repertoire of antigenic variants resistant to a neutralizing monoclonal antibody., The altered repertoire includes variants with substitutions at the Arg-Gly-Asp motif, Mutants lacking this sequence replicated normally in cell culture and were indistinguishable from the parental virus. Studies with individual FMDV clones indicate that amino acid replacements on the capsid surface located around the loop harboring the Arg-Gly-Asp triplet mag mediate in the dispensability of this motif. The results show that FMDV quasispecies evolving in a constant biological environment have the capability of rendering totally dispensable a receptor recognition motif previously invariant, and to ensure an alternative pathway for normal viral replication, Thus, variability of highly conserved motifs, even those that viruses have adapted from functional cellular motifs, can contribute to phenotypic flexibility of RNA viruses in nature.