title: Single amino acid substitution of VP1 N17D or VP2 H145Y confers acid-resistant phenotype of type Asia1 foot-and-mouth disease virus.
abstract: Infection by foot-and-mouth disease virus (FMDV) is triggered by the acidic pH in endosomes after virus uptake by receptor-mediated endocytosis. However, dissociation of the FMDV 146S particle in mildly acidic conditions renders inactivated foot-and-mouth disease (FMD) vaccines much less effective. Type Asia1 FMDV mutants with increased resistance to acid inactivation were selected to study the molecular basis of viral resistance to acid-induced disassembly and improve the acid stability of FMDV. Sequencing of capsid-coding regions revealed four amino acid replacements (VP1 N17D, VP2 H145Y, VP2 G192D, and VP3 K153E) in the viral population of the acid-selected 10th passage. We performed single or combined mutagenesis using a reverse genetic system, and our results provide direct experimental evidence that VP2 H145Y or VP1 N17D substitution confers an acid-resistant phenotype to type Asia1 FMDV.
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Song
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Zeng
authors.forename: Guohui
authors.initials: G
authors.lastname: Zhou
authors.forename: Decheng
authors.initials: D
authors.lastname: Yang
authors.forename: Te
authors.initials: T
authors.lastname: Liang
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000143:Acids / Q000633:toxicity*; D019943:Amino Acid Substitution; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D024882:Drug Resistance, Viral; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000502:physiology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D059386:Reverse Genetics; D012692:Serial Passage; D014776:Virus Cultivation
chemical_list: D000143:Acids; D036022:Capsid Proteins; D050505:Mutant Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; C442459:VP2 protein, Foot-and-mouth disease virus
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