Sequence analysis of capsid coding region of foot-and-mouth disease virus type A vaccine strain during serial passages in BHK-21 adherent and suspension cells

Sequence variability within the capsid coding region of the foot-and-mouth disease virus type A vaccine strain during serial in vitro passage was investigated. Specifically, two methods of virus propagation were utilized, a monolayer and suspension culture of BHK-21 cells. At three positions (VP2131 E-K in both monolayer and suspension passages, VP385 H-R in late monolayer passages and VP3139 K-E in only suspension passages), all mapped to surface exposed loops, amino acid substitutions were apparently fixed without reversion till the end of the passage regime. Interestingly, VP2131, 121 and VP385 which form part of the heparan sulphate binding pocket, showed a tendency to acquire positively charged amino acids in either monolayer or suspension environment probably to better interact with the negatively charged cell surface glycosaminoglycans. At three identified antigenically critical positions (VP279, VP3139 and VP1154), amino acids substitutions even in the absence of immune pressure were noticed. Hence both random drift and adaptive mutations attributable to the strong selective pressure exerted by the proposed cell surface alternate receptors could play a role in modifying the capsid sequence of cell culture propagated FMDV vaccine virus, which in turn may alter the desired potency of the vaccine formulations.