title: 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 (L(pro)) and 3A proteins were the most variable whilst the RNA-dependent RNA polymerase (3D(pol)) the most conserved. Phylogeny based on the non-structural protein-coding regions showed separate clusters for southern African viruses for both the L(pro) and 3C protease (3C(pro)) and sequences unique to this group of viruses, e.g. in the 2C and 3C(pro) 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 L(pro) 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 (3C(pro)) and 3D(pol) showed that the observed variation does not affect the enzymatic active sites or substrate binding sites. Variation in the 3C(pro) cleavage sites demonstrates broad substrate specificity.
authors.affiliation: Agricultural Research Council, Onderstepoort Veterinary Institute, Transboundary Animal Diseases Programme, Private Bag X05, Onderstepoort 0110, South Africa; Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.
authors.forename: P
authors.initials: P
authors.lastname: Nsamba
authors.affiliation: European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom.
authors.forename: T A P
authors.initials: TA
authors.lastname: de Beer
authors.affiliation: Agricultural Research Council, Onderstepoort Veterinary Institute, Transboundary Animal Diseases Programme, Private Bag X05, Onderstepoort 0110, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Chitray
authors.affiliation: Agricultural Research Council, Onderstepoort Veterinary Institute, Transboundary Animal Diseases Programme, Private Bag X05, Onderstepoort 0110, South Africa.
authors.forename: K
authors.initials: K
authors.lastname: Scott
authors.affiliation: Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa; CSIRO-Australian Animal Health Laboratory, Private Bag 24, Geelong 3220, VIC, Australia.
authors.forename: W
authors.initials: W
authors.lastname: Vosloo
authors.affiliation: Agricultural Research Council, Onderstepoort Veterinary Institute, Transboundary Animal Diseases Programme, Private Bag X05, Onderstepoort 0110, South Africa; Department of Microbiology and Plant Pathology, Faculty of Agricultural and Natural Sciences, University of Pretoria, Pretoria 0002, South Africa. Electronic address: mareef@arc.agric.za.
authors.forename: F F
authors.initials: FF
authors.lastname: Maree
mesh_terms: D017954:Africa South of the Sahara; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D010450:Endopeptidases / Q000235:genetics; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics*; D014644:Genetic Variation; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics*
chemical_list: D017361:Viral Nonstructural Proteins; D012324:RNA-Dependent RNA Polymerase; D010450:Endopeptidases
keywords: 3A-protein; 3B/Vpg-protein; 3C-protease, RNA-dependent RNA polymerase; Foot-and-mouth disease virus; Leader-protease, 2C/AAA+ ATPase; Non-structural proteins