title: Selection and characterization of an acid-resistant mutant of serotype O foot-and-mouth disease virus.
abstract: Foot-and-mouth disease virus (FMDV) loses infectivity and immunogenicity due to its disassembly in culture environments below pH 6.8. To study the molecular basis of viral resistance to acid-induced disassembly and improve the acid stability of inactivated FMD vaccines during the manufacturing process, type O FMDV mutants with increased resistance to acid inactivation were selected, and the genes encoding their capsid proteins were sequenced. Three amino acid substitutions (VP1 N17D, VP2 D86A, and VP4 S73N) were found in all of the mutants. When these substitutions were introduced into seven infectious FMDV clones alone or combined, a single amino acid substitution in the VP1 protein, N17D, which also appears in type C FMDV acid-resistant mutants, was found to be responsible for the increased resistance to acid inactivation for type O FMDV. In addition, although viral fitness was reduced under standard culture conditions, viral growth kinetics and virulence were not significantly altered in the rescued mutant virus rN17D with the VP1 N17D substitution. Importantly, the N17D substitution could confer improved immunogenicity to the mutant virus rN17D under acidic conditions compared with its parental virus O/YS/CHA/05. These results demonstrate that the N17D substitution in VP1 is the molecular determinant of the acid-resistant phenotype in type O FMDV, indicating the potential for use of this substitution to improve the acid stability of inactivated FMD vaccines during the vaccine production process.
authors.forename: Te
authors.initials: T
authors.lastname: Liang
authors.forename: Decheng
authors.initials: D
authors.lastname: Yang
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Jingfei
authors.initials: J
authors.lastname: Wang
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Song
authors.forename: Guohui
authors.initials: G
authors.lastname: Zhou
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; D002460:Cell Line; D006224:Cricetinae; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral; D029544:Foot-and-Mouth Disease Virus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D050296:Microbial Viability / Q000187:drug effects*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D014774:Virulence; D014776:Virus Cultivation; D014779:Virus Replication
chemical_list: D000143:Acids; D036022:Capsid Proteins