Single Amino Acid Substitutions Surrounding the Icosahedral Fivefold Symmetry Axis Are Critical for Alternative Receptor Usage of Foot-and-Mouth Disease Virus

文献类型： 外文期刊

第一作者： Gong, Xiao-Hua

作者： Gong, Xiao-Hua;Bai, Xing-Wen;Li, Ping-Hua;Bao, Hui-Fang;Zhang, Meng;Chen, Ying-Li;Sun, Pu;Yuan, Hong;Huang, Lei;Ma, Xue-Qing;Fu, Yuan-Fang;Cao, Yi-Mei;Li, Kun;Zhang, Jing;Li, Zhi-Yong;Li, Dong;Lu, Zeng-Jun;Liu, Zai-Xin

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关键词： foot-and-mouth disease virus; alternative cellular receptors; site-directed mutations; phenotypic properties; integrin-independent endocytic pathway

期刊名称：VIRUSES-BASEL （ 影响因子：5.048； 五年影响因子：5.127 ）

ISSN：

年卷期： 2020 年 12 卷 10 期

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收录情况： SCI

摘要： The integrins function as the primary receptor molecules for the pathogenic infection of foot-and-mouth disease virus (FMDV) in vivo, while the acquisition of a high affinity for heparan sulfate (HS) of some FMDV variants could be privileged to facilitate viral infection and expanded cell tropism in vitro. Here, we noted that a BHK-adapted Cathay topotype derivative (O/HN/CHA/93tc) but not its genetically engineered virus (rHN), was able to infect HS-positive CHO-K1 cells and mutant pgsD-677 cells. There were one or three residue changes in the capsid proteins of O/HN/CHA/93tc and rHN, as compared with that of their tissue-originated isolate (O/HN/CHA/93wt). The phenotypic properties of a set of site-directed mutants of rHN revealed that E83K of VP1 surrounding the fivefold symmetry axis was necessary for the integrin-independent infection of O/HN/CHA/93tc. L80 in VP2 was essential for the occurrence of E83K in VP1 during the adaptation of O/HN/CHA/93wt to BHK-21 cells. L80M in VP2 and D138G in VP1 of rHN was deleterious, which could be compensated by K83R of VP1 for restoring an efficient infection of integrin-negative CHO cell lines. These might have important implications for understanding the molecular and evolutionary mechanisms of the recognition and binding of FMDV with alternative cellular receptors.

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