Engineering Responses to Amino Acid Substitutions in the VP0- and VP3-Coding Regions of PanAsia-1 Strains of Foot-and-Mouth Disease Virus Serotype O.

摘要: The presence of sequence divergence through adaptive mutations in the major capsid protein VP1, and also VP0 (VP4 VP2) VP3, foot-and-mouth disease virus (FMDV) is relevant to a broad range viral characteristics. To explore potential role isolate-specific residues VP3 coding regions PanAsia-1 strains genetic phenotypic properties FMDV, series recombinant full-length genomic clones were constructed using Cathay topotype infectious cDNA as original backbone. deleterious compensatory effects individual amino acid substitutions at positions 4008 3060 several different domains VP2 illustrated that chain-based spatial interaction patterns VP2, (VP1-3), well between internal VP4 three external proteins might contribute assembly eventually viable viruses. Y2079H site-directed mutants dramatically induced decrease plaque size on BHK-21 cells pathogenicity suckling mice. Remarkably, 2079H-encoding viruses displayed moderate increase sensitivity correlated with NH4Cl resistance compared Y2079-encoding Interestingly, none all 16 rescued able infect heparan sulfate-expressing CHO-K1 cells. However, infection was facilitated by utilizing non-integrin-dependent, heparin-sensitive receptor(s) replacements four uncharged acids position 3174 FMDV had no apparent influence heparin affinity. These results provide particular insights into correlation evolutionary biology diversity adapting populations FMDV.IMPORTANCE variation within occurs frequently susceptible tissue cultures, reflecting high levels FMDV. A systematic study for functional significance suggested side chains N terminus VP1-3 cascading viability developmental characteristics progeny indicated FMDVs could affect pathogenicity, resistance, whereas there inevitable acid-sensitive phenotypes. affinity non-integrin-dependent be explained differences structures sulfate proteoglycans surfaces cell lines. may our understanding distinct vitro vivo.