Abstract
Three lineages of serotype O of foot-and-mouth disease virus were passaged serially in BHK-21 cell culture without application of any immune pressure, to study the frequency, nature and location of the substitutions accruing on the virus capsid. The viruses showed unusual stability as only 12 substitutions were observed in 13 different regimens and the majority of the substitutions reverted back to the parental genotype very soon after their appearance. Of the 12 substitutions, a maximum of 8 were found in the VP1 region. Some substitutions (81, 147, 152, 203 and 210 in VP1 and 50 in VP3) were observed at the established antigenic sites suggesting that antigenic diversification can occur in the absence of immune selection. The viruses after serial cytolytic infection of BHK-21 cells, demonstrated an ability to infect the integrin-deficient CHO-K1 cell line suggesting an expansion in their receptor usage potential. Even after 25–50 passages in BHK-21 cell system no histidine to arginine switch was observed at the 56th residue of VP3. Amino acid sequence analysis of 141 Indian field isolates for the residues involved in heparin binding sites suggest the importance of net positive charge in the HS-binding pocket or elsewhere on the capsid for interaction with the alternative receptors and cell culture adaptation rather than acquisition of positive charge at any particular position for all serotype O strains.
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Acknowledgements
The authors are thankful to Indian Council of Agricultural Research for providing necessary facilities to carry out this work. The first author is thankful to ICAR for providing senior research fellowship during his doctoral degree.
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Significance Statement The study reports substitutions observed in serial passage of FMDV in the cell culture without immune pressure and discussed their significance. The study suggests the importance of net positive charge in the HS-binding pocket or elsewhere on the capsid for interaction with the alternative receptors and cell culture adaptation rather than acquisition of positive charge at any particular position for all serotype O strains.
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Sarangi, L.N., Mohapatra, J.K., Subramaniam, S. et al. Substitutions accrued on Foot-and-mouth disease virus capsid during propagation in cell culture. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 89, 747–753 (2019). https://doi.org/10.1007/s40011-018-0986-9
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DOI: https://doi.org/10.1007/s40011-018-0986-9