Determination of common genetic variants within the non-structural proteins of foot-and-mouth disease viruses isolated in sub-Saharan Africa

Abstract

The non-structural proteins of foot-and-mouth disease virus (FMDV) are responsible for RNA replication, proteolytic processing of the viral polyprotein precursor, folding and assembly of the structural proteins and modification of the cellular translation apparatus. Investigation of the amino acid heterogeneity of the non-structural proteins of seventy- nine FMDV isolates of SAT1, SAT2, SAT3, A and O serotypes revealed between 29 and 62% amino acid variability. The Leader protease (Lpro) and 3A proteins were the most variable whilst the RNA-dependent RNA polymerase (3Dpol) the most conserved. Phylogeny based on the non-structural protein-coding regions showed separate clusters for southern African viruses for both the Lpro and 3C protease (3Cpro) and sequences unique to this group of viruses, e.g. in the 2C and 3Cpro proteins. These groupings were unlike serotype groupings based on structural protein-coding regions. The amino acid substitutions and the nature of the naturally occurring substitutions provide insight into the functional domains and regions of the non-structural proteins that are critical for structure–function. The Lpro of southern African SAT type isolates differed from A, O and SAT isolates in northern Africa, particularly in the auto-processing region. Three-dimensional structures of the 3C protease (3Cpro) and 3Dpol showed that the observed variation does not affect the enzymatic active sites or substrate binding sites. Variation in the 3Cpro cleavage sites demonstrates broad substrate specificity.