Abstract
Elucidation of the molecular basis of the stability of foot-and-mouth disease virus (FMDV) particles is relevant to understand key aspects of the virus cycle. Residue N17D in VP1, located at the capsid inner surface, modulates the resistance of FMDV virion to dissociation and inactivation at acidic pH. Here we have studied whether the virion-stabilizing effect of amino acid substitution VP1 N17D may be mediated by the alteration of electrostatic charge at this position and/or the presence of the viral RNA. Substitutions that either introduced a positive charge (R,K) or preserved neutrality (A) at position VP1 17 led to increased sensitivity of virions to inactivation at acidic pH, while replacement by negatively charged residues (D,E) increased the resistance of virions to acidic pH. The role in virion stability of viral RNA was addressed using FMDV empty capsids that have a virtually unchanged structure compared to the capsid in the RNA-filled virion, but that are considerably more resistant to acidic pH than WT virions, supporting a virion-destabilizing effect of the RNA. Remarkably, no differences were observed in the resistance to dissociation at acidic pH between the WT empty capsids and those harboring replacement N17D. Thus, the virion-destabilizing effect of viral RNA at acidic pH can be partially restored by introducing negatively charged residues at position VP1 N17.
Highlights
Elucidation of the molecular basis of the stability of foot-and-mouth disease virus (FMDV) particles is relevant to understand key aspects of the virus cycle
Minor variations in the plaque size of N17 mutants was observed, with mutants VP1 N17D, VP1 N17E and VP1 N17A showing a slight decrease in diameter (Fig. 1A) as that observed for VP1 N17D + VP2 H145Y, a highly acid-stable mutant selected by acidic incubation from mutant N17D23
We have demonstrated that replacement of amino acid residue VP1 N17 by a positively charged residue (K,R) or truncation of its side chain (A) decrease the resistance of FMDV virions to inactivation at acidic pH
Summary
Elucidation of the molecular basis of the stability of foot-and-mouth disease virus (FMDV) particles is relevant to understand key aspects of the virus cycle. In serotype C FMDV residue 17 of VP1 is located only about 15 and 8 Å, respectively, from H140 and H143 in VP3 of the same protomer Protonation of these residues has been proposed to exert an electrostatic repulsion with the dipole of an alpha helix in the neighbouring pentamer, facilitating capsid dissociation within the acidic environment of the endosome[28,29]. In this context, it was hypothesized that the negative charge introduced in mutant VP1 N17D could partially neutralize the positive charge of the protonated VP3 H143, reducing the interpentamer repulsion at acidic pH and leading to increased resistance against acid-induced dissociation into pentamers[22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
