Evolution of DS-1-like G8P[8] rotavirus A strains from Vietnamese children with acute gastroenteritis (2014–21): Adaptation and loss of animal rotavirus-derived genes during human-to-human spread

Figure 1.. The workflow of the experiments to determine electropherotypes and genotype/lineage constellations of G8P[8] strains.

Figure 2.. Molecular epidemiology and evolutionary changes of DS-1-like G8P[8] rotavirus A strains, 2014–21: A hypothesis on the fate of the animal RVA-derived genes during the process of adaptation to the human host. (A) The circulation was divided into two waves of prevalence, with the first between 2014 and 2017, and the second between 2018 and 2021. The detection rate of G8P[8] is defined as the number of positive samples with G8P[8] divided by the total number of samples genotyped in each year. (B) The shift in the genome constellation agreed well with two waves of G8P[8] prevalence. (C) It was speculated that a bovine-like G8 strain jumped into humans between 2009 and 2012.The strains dominant during the first wave had three animal RVA-derived backbone genes but the strains dominant during the second wave expelled all these animal genes, comprising fully human RVA genes except the G8 VP7 gene. Mutational changes were observed in neutralisation epitopes of VP7 and VP8* concurrent with the two waves of G8P[8] prevalence, but none of these sites appeared to be positively selected.

Figure 3.. Genetic analyses on full-genome sequences that were made by merging the eleven CDS of the eleven gene segments of DS-1-like G8P[8] strains from Vietnam and elsewhere in the world. (A) A ML subtree was constructed from which two outgroups (Wa and AU-1) were excluded. The bootstrap values less than 90 per cent were hidden. The branch lengths were scaled to the genetic distance defined as the number of substitutions per site. The G8P[8] strains possessing constellation A were displayed with triangles and those possessing constellation E with squares. (B) Histogram of pairwise-distances (p-distances) between the full-genome sequences of Vietnamese G8P[8] strains possessing constellations A and E. The p-distances were significantly separated into two categories: (1) within constellation A (0.1–1 per cent) and E (0–2.4 per cent), respectively; (2) between constellations A and E (4.3–5.5 per cent).

Figure 4.. The time-scaled phylogenetic tree for the VP7 gene, estimating the time of emergence, and the spread of bovine-like G8 RVAs into human population. The interspecies transmission of bovine-like RVAs into human occurred sometime between 2009 and 2012, and that there were Thai G8P[8] strains that preceded the similar strains detected in Vietnam in 2014. The 22-year timescale (i.e. 1999–2021) was indicated below the tree.

Figure 5.. Evaluation of recombination event occurring on the CDS of VP7 of strain RVN17-0178, using the RDP4.101 BetaBig: (A) recombination information; (B) the recombination event was confirmed by five detection methods: RDP, Geneconv, MaxChi, Chimæra, and 3Seq. (C) Recombination graphic; (D) visualisation of evidence of recombination using RDP4.101 BetaBig tool.

Figure 6.. Hypothesis on the fate of animal RVA-derived genes of spillover animal RVAs during human-to-human spread. The vast majority of cases result in dead-end infections without further implication for rotavirus evolution. In much smaller proportion of cases, there may be some degree of onward, human-to-human transmission, during which the spillover virus must undergo reassortment with a co-infecting human virus and exchange of cognate genes to achieve ‘humanisation’ of the animal rotavirus genome. During the ‘adaptation’ process to the human host occurs the expulsion of animal RVA-derived genes from the genome of the progeny of the original spillover virus.