Molecular phylogeny of leader proteinase gene of type A of Foot-and-mouth disease virus from India.

We previously demonstrated the presence of three genotypes (IV, VI and VII) of type A (subtype A22) of Foot-and-mouth disease virus (FMDV) in India based on 1D gene sequence analysis. In the present study, the leader proteinase (L(pro)) gene sequences of 35 type A FMDV field isolates sampled over a period of 24 years (1977-2000) have been analyzed. Maximum-likelihood (ML) phylogenetic analysis revealed four distinct genetic lineages (A-D), indicating high divergence in L gene of type A FMDV. Lineages A and D correspond to the earlier genotypes IV, and VII, respectively. The genotype VI isolates were divided into two separate lineages (B and C) in the tree with high confidence values (96-99%). One isolate (IND 21/90) showed incongruous grouping between the (1D and L) gene-based analyses, which could be due to intergenotypic recombination. The ML molecular clock hypothesis was easily rejected on the data set studied indicating the absence of clock-like evolution in the L gene. ML codon-substitution models identified positive selection in the amino acid site 194 of C-terminal extension of the Lb(pro) with high posterior probability (>99%). The catalytic triad of the L(pro) at C-51, H-148 and D-163 were conserved across all the Indian isolates studied. Finally, amino acid differences between the lineages have been discussed briefly.