title: Genetic heterogeneity in the foot-and-mouth disease virus Leader and 3C proteinases.
abstract: The Leader and 3C proteinases of foot-and-mouth disease virus (FMDV) are responsible for almost all the proteolytic processing events of the viral polyprotein precursor. Investigation into the genetic heterogeneity of the regions encoding these proteins from isolates of six FMDV serotypes revealed the 3C proteinase to be more conserved than the Leader proteinase. Maximum likelihood analysis indicated similar phylogenetic groupings for the non-structural protein coding regions of both the Leader and 3C. These groupings were different from the structural VP1 protein coding region which, as shown previously, grouped according to serotype. Two distinct clades were apparent for both the Leader and 3C coding regions: one comprising of serotypes A, O and C together with SAT (South African Territories) isolates from eastern Africa. The other clade consisted of SAT isolates originating from southern Africa. Only one virus isolate, obtained from a buffalo in Uganda, did not conform to this phylogenetic pattern. This SAT 1 virus grouped with types A, O and C in the Leader analysis, but with the southern African SAT types in the 3C analysis, implicating intertypic recombination. The leader proteinases of southern African SAT type isolates differed from those present in European type isolates, particularly in the self-processing region. A three-dimensional structure was modeled for the Leader proteinase of one of the SAT type viruses, ZIM/7/83/2, and compared with the previously elucidated crystal structure of O(1)Kaufbeuren Leader proteinase. The active sites of the two leaders were found to superimpose closely, despite the observed sequence variation between the two molecules. Comparison of the 3C proteinase P1 cleavage sites suggested that the FMDV 3C proteinase may possess a broader substrate specificity, as observed in hepatitis A virus 3C proteinase.
authors.affiliation: Exotic Diseases Division, Onderstepoort Veterinary Institute, Private Bag X05, Onderstepoort 0110, South Africa. trudi@saturn.ovi.ac.za
authors.forename: Hester
authors.initials: H
authors.lastname: van Rensburg
authors.forename: Daniel
authors.initials: D
authors.lastname: Haydon
authors.forename: Fourie
authors.initials: F
authors.lastname: Joubert
authors.forename: Armanda
authors.initials: A
authors.lastname: Bastos
authors.forename: Livio
authors.initials: L
authors.lastname: Heath
authors.forename: Louis
authors.initials: L
authors.lastname: Nel
mesh_terms: D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D002213:Capsid / Q000235:genetics; D036022:Capsid Proteins; D003546:Cysteine Endopeptidases / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics*; D018740:Genetic Heterogeneity; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D036022:Capsid Proteins; D018076:DNA, Complementary; C442501:VP1 protein, Foot-and-mouth disease virus; D014764:Viral Proteins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; C088747:leader proteinase, foot-and-mouth disease virus