Phylogeny, genome evolution, and antigenic variability among endemic foot-and-mouth disease virus type A isolates from India

The capsid-coding (P1) and 3A regions of foot-and-mouth disease virus (FMDV) type A field isolates including two vaccine strains collected during 1977-2000 were analyzed. In the phylogenies, the isolates were distributed into two previously identified genotypes VI and VII, with multiple sub-genotypes that are temporally clustered. Comparison of the antigenic relationships of field isolates with the two vaccine strains (IND 17/77 and IND 490/97) and the reference strains of the genotypes VI (IND 233/99) and VII (IND 40/00) indicated two broad antigenic groups that correlate with the phylogenetic groupings (genotypes VI and VII), and are highly divergent from the vaccine strains. The maximum likelihood method of selection analysis identified a number of amino acid sites within the P1 region to be under weak positive selection. Some of the positively selected sites were mapped at/near the antigenically critical amino acid sites of the P1 region, indicating host immune pressure as one of the important driving force behind the observed genetic and antigenic diversity in FMDV. A small number of selected sites are located in the heparan sulphate-binding pocket of the virus, suggesting a fitness advantage for cell entry of the virus. No positive selection was detected in the 3A dataset.