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

Gong, XH; Bai, XW; Li, PH; Bao, HF; Zhang, M; Chen, YL; Sun, P; Yuan, H; Huang, L; Ma, XQ; Fu, YF; Cao, YM; Li, K; Zhang, J; Li, ZY; Li, D; Lu, ZJ; Liu, ZX

Bai, XW; Liu, ZX (corresponding author), Chinese Acad Agr Sci, State Key Lab Vet Etiol Biol, Lanzhou Vet Res Inst, OIE China Natl Foot & Mouth Dis Reference Lab, Lanzhou 730046, Peoples R China.

VIRUSES-BASEL, 2020; 12 (10):


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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