Single Amino Acid Substitutions Surrounding the Icosahedral Fivefold Symmetry Axis Are Critical for Alternative Receptor Usage of Foot-and-Mouth Disease Virus
Xiao-Hua Gong,
Xing-Wen Bai,
Ping-Hua Li,
Hui-Fang Bao,
Meng Zhang,
Ying-Li Chen,
Pu Sun,
Hong Yuan,
Lei Huang,
Xue-Qing Ma,
Yuan-Fang Fu,
Yi-Mei Cao,
Kun Li,
Jing Zhang,
Zhi-Yong Li,
Dong Li,
Zeng-Jun Lu,
Zai-Xin Liu
Affiliations
Xiao-Hua Gong
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Xing-Wen Bai
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Ping-Hua Li
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Hui-Fang Bao
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Meng Zhang
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Ying-Li Chen
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Pu Sun
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Hong Yuan
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Lei Huang
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Xue-Qing Ma
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Yuan-Fang Fu
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Yi-Mei Cao
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Kun Li
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Jing Zhang
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Zhi-Yong Li
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Dong Li
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Zeng-Jun Lu
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Zai-Xin Liu
State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
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.
