Mutation in the 1D gene (VP1) of Foot-and-mouth disease virus serotype Asia1 during serial cytolytic infections in cell culture

Abstract

Changes in the nucleotide sequence of the 1D gene of two vaccine strains (IND 63/72 and IND 491/97) of Foot-and-mouth disease virus (FMDV) serotype Asia1 during serial cytolytic infections in cell culture have been analyzed. Sequence comparisons revealed a majority of transition mutations in IND 491/97. The mutation frequency of the 1D gene of IND 491/97 was about 4.5 to 6.0 fold higher than that of IND 63/72. At the amino acids 40-60 and 140-160 regions the mutation frequency was higher compared to the whole VP1. Both viruses showed a constant change at certain residues of the G-H loop region with an accumulation of amino acid replacements during serial cytolytic passages in cell culture. The critical residues (145 and 153) identified previously using mAbs recognizing trypsin-sensitive epitopes were not substituted in the absence of immune selection but changes were observed at positions 142 and 148. Non-reactivity of IND 63/72 after 50(th) passage level onwards with a panel of mAbs indicated an alteration in the antigenic specificity of the virus. Comparison of amino acid sequences in the entire capsid coding region of the naturally occurring field isolates with that of the 50(th) and 100(th) passage level viruses of IND 63/72 revealed that the residues 56 and 74 of VP2 could be involved in mAb binding. The results suggest that fixation of amino acid replacements occurs in VP1 of Asia1 virus, which could play an important role in antigenic variation by modulating different antigenic epitopes located on the surface of the virus.