Feline Rotavirus A as a Source of Spillover Infections to Humans: An In-Depth Analysis of Molecular Epidemiological...

Rotavirus A (RVA) is a leading cause of severe diarrhoea in children, and interspecies transmission significantly drives the genomic diversity of human RVAs. Cats represent a key host species, requiring in-depth analysis regarding RVA transmission to humans. This review evaluated the literature on the complex genotype constellations of feline RVAs in relation to relevant canine and human RVAs to define the role of feline RVAs in the evolutionary history of human strains. The review traces the methodological shift from genogrouping by RNA-RNA hybridisation to the current genotype constellation system enabled by whole-genome sequencing. While early methods identified a shared genomic closeness between human AU-1 and feline FRV-1, whole-genome sequencing indicated that several human RVA strains, including AU-1, HCR3A, and Ro1845, likely resulted from direct transmission of feline/canine strains, due to shared genotype constellations and high sequence identity with animal strains like feline FRV-1, Cat97 and canine CU-1. Evidence of reassortment-such as the emergence of G1P[9] and G9P[9] strains after the feline-derived G3P[9] crossed into the human population-suggests these feline-like strains have successfully overcome the host-species barrier and are capable of onward human-to-human transmission, not just dead-end spillover events. However, definitive confirmation of sustained transmission or contemporary spillover requires stringent phylogenetic criteria: multiple human strains with >99% identical sequences in a monophyletic lineage for sustained transmission, or an identical human-feline pair across all genome segments for contemporary spillover. Confirming the status of the AU-1-like constellation as a third, low-frequency human RVA type requires future studies applying these strict criteria.