The 3C protease region of FMDV-A isolates from India shows high conservation and incongruous phylogenetic grouping compared to the VP1 region, suggesting potential for a vaccine-exploitable T-cell epitope.
May support 3Cpro as a conserved T-cell epitope target for FMDV vaccines; leaves open functional validation in vivo.
Nucleotide sequence analysis of the 3C protease (3C(pro)) region of Foot-and-mouth disease virus type A (FMDV-A) isolates from India has revealed incongruous phylogenetic grouping between 3C(pro) and VP1 region possibly due to the genetic recombination or independent evolution of non-structural and structural protein coding regions. Similar to the VP1 region, the emerging VP3(59)-deletion group maintained its genetic distinctiveness at 3C(pro) region and was found to be diverging with time. Two lineage specific signature aa residues were detected for the deletion group in proof of lineage specific drift or selection events. 3C(pro) region exhibited high degree of conservation as evident from low dN/dS ratio (0.036) and percentage of variable aa positions (20%). A transmembrane domain from aa 27 to 44 could be predicted that possibly anchors 3C to intracellular membranes for better interaction with RNA replication complex. On the basis of sequence conservation, the likelihood that the region aa 121-150 was carrying a vaccine exploitable T-cell epitope was very high.
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Mohapatra et al. (2009) studied this question.
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