ᅟ: This review summarized the molecular determinants of the acid stability of FMDV in order to explore the uncoating mechanism of FMDV and improve the acid stability of vaccines.
Background: The foot-and-mouth disease virus (FMDV) capsid is highly acid labile and tends to dissociate into pentameric subunits at acidic condition to release viral RNA for initiating virus replication. However, the acid stability of virus capsid is greatly required for the maintenance of intact virion during the process of virus culture and vaccine production. The conflict between the acid lability in vivo and acid stability in vitro of FMDV capsid promotes the selection of a series of amino acid substitutions which can confer resistance to acid-induced FMDV inactivation. In order to explore the uncoating activity of FMDV and enhance the acid stability of vaccines, we summarized the available works about the pH stability of FMDV. In this review, we analyzed the intrinsic reasons for the acid instability of FMDV from the structural and functional aspects. We also listed all substitutions obtained by different research methods and showed them in the partial capsid of FMDV. We found that a quadrangle region in the viral capsid was the place where a great many pH-sensitive residues were distributed. As the uncoating event of FMDV is dependent on the pH-sensitive amino acid residues in the capsid, this most pH-sensitive position indicates a potential candidate location for RNA delivery triggered by the acid-induced coat disassociation.
Short conclusion: This review provided an overview of the pH stability of FMDV. The study of pH stability of FMDV not only contributes to the exploration of molecule and mechanism information for FMDV uncoating, but also enlightens the development of FMDV vaccines, including the traditionally inactivated vaccines and the new VLP (virus-like particle) vaccines.
Keywords: FMDV; Substitutions; Uncoating; pH stability.