The occurrence of amino acid substitutions D96N and S242N in VP7 of emergent G2P[4] rotaviruses in Nepal in 2004-2005: a global and evolutionary perspective

Rotavirus is the leading cause of severe diarrhea among children worldwide. Strains with G2P[4] have captured recent attention because of its abrupt increase or re-emergence in many locations in the world. In Nepal, G2P[4] strains were detected at a rate of 1% in 2003-2004, but increased to 33% in 2004-2005. Thus, the VP7 genes of 45 emergent G2 strains from Nepal were sequenced and analyzed together with a total of 339 G2VP7 sequences detected over the last 34 years that were compiled from the DNA database. We found that all Nepalese VP7 sequences had a substitution from aspartic acid to asparagine at residue 96 (D96N) that was the hallmark of the lineage termed sublineage IVa, which replaced virtually all globally circulating G2 strains during the last decade. Within sublineage IVa, further sublineages emerged, of which a sublineage termed IVa-3 was identified to have another amino acid substitution from serine to asparagine at 242 (S242N). This sublineage, to which all Nepalese sequences belonged, now became the most frequent G2 sequence globally. In conclusion, the G2VP7 gene evolved in a dynamic fashion such that new lineages emerged within the previously dominant lineage, one of which became subsequently dominant.