Abstract:
The transient upsurge of G2P[4] group A rotavirus (RVA) after Rotarix vaccine introduction in several countries has been a
matter of concern. To gain insight into the diversity and evolution of G2P[4] strains in South Africa pre- and post-RVA
vaccination
introduction, whole-genome
sequencing was performed for RVA positive faecal specimens collected between 2003
and 2017 and samples previously sequenced were obtained from GenBank (n=103; 56 pre- and 47 post-vaccine).
Pre-vaccine
G2 sequences predominantly clustered within sub-lineage
IVa-1.
In contrast, post-vaccine
G2 sequences clustered mainly
within sub-lineage
IVa-3,
whereby a radical amino acid (AA) substitution, S15F, was observed between the two sub-lineages.
Pre-vaccine
P[4] sequences predominantly segregated within sub-lineage
IVa while post-vaccine
sequences clustered mostly
within sub-lineage
IVb, with a radical AA substitution R162G. Both S15F and R162G occurred outside recognised antigenic sites.
The AA residue at position 15 is found within the signal sequence domain of Viral Protein 7 (VP7) involved in translocation of
VP7 into endoplasmic reticulum during infection process. The 162 AA residue lies within the hemagglutination domain of Viral
Protein 4 (VP4) engaged in interaction with sialic acid-containing
structure during attachment to the target cell. Free energy
change analysis on VP7 indicated accumulation of stable point mutations in both antigenic and non-antigenic
regions. The
segregation of South African G2P[4] strains into pre- and post-vaccination
sub-lineages
is likely due to erstwhile hypothesized
stepwise lineage/sub-lineage
evolution of G2P[4] strains rather than RVA vaccine introduction. Our findings reinforce the need
for continuous whole-genome
RVA surveillance and investigation of contribution of AA substitutions in understanding the
dynamic G2P[4] epidemiology.
