Interspecies Transmission of Animal Rotaviruses to Humans: Reassortment-Driven Adaptation

Rotavirus alphagastroenteritidis (rotavirus) infects a broad range of hosts, including humans and various animal species. Its genome comprises 11 segments of double-stranded RNA, making it highly prone to genetic diversity through gene reassortment. Although rotavirus strains are typically host-specific, novel human strains with global impact often originate from interspecies transmission of animal rotaviruses. This review explores the critical role of interspecies transmission coupled with genetic reassortment in rotavirus adaptation to humans, contextualizing key studies and methodological advances. Central to this progress was the development of tools to analyse entire genomes and distinguish homologous from heterologous strains. We trace the evolution from RNA-RNA hybridisation to whole-genome sequencing, which underpins genotype constellation and sub-genotype phylogeny. A decade-long surveillance of the bovine-like G8 rotavirus in Vietnam offers a compelling model: for an animal rotavirus to become a successful human pathogen, it must replace its animal-derived genes with human-derived counterparts through reassortment. Retaining the animal-origin G8 VP7 gene is enabled by acquiring a compatible human VP4 gene (specifically P[8]) and DS-1-like backbone genes. Building on this model of reassortment-driven adaptation, our investigation into the unusual G1P[6] strain AU19, of wholly porcine origin, supports the hypothesis that the predominant human G1 rotavirus also evolved from a successful interspecies transmission event. Phylogenetic analysis suggests the ancestral human G1 gene emerged from a porcine rotavirus between 1915 and 1948, later reassorting with human strains to acquire Wa-like backbone genes, ultimately becoming a stable and dominant part of the human rotavirus population. In conclusion, genetic reassortment is a key mechanism transforming sporadic zoonotic events into sustained human-pathogens, although other factors remain to be fully defined. We conclude by highlighting key areas for further research.