Factors contributing to the frequent interspecies transmission of G4P[6] Rotavirus alphagastroenteritidis strains from pigs to humans in Vietnam: molecular epidemiological insights

In parts of Asia, including Vietnam, Rotavirus alphagastroenteritidis (formerly known as Rotavirus A ; RVA) strains of porcine origin, particularly G4P[6] strains, have been detected in humans at relatively high frequencies. This study investigated the origins of G4P[6] strains identified in Vietnamese children and examined possible factors underlying their frequent detection, based on molecular epidemiological analyses. Among the 1,252 RVA-positive faecal specimens collected over a 2-year period, 28 (2.2%) contained only the G4P[6] strain. Of these, 23 (1.8%) G4P[6] strains were successfully sequenced for their whole genomes, all of which were confirmed to be entirely of porcine RVA origin, with no evidence of genomic reassortment with human RVA strains. Two distinct clusters of G4P[6] strains (comprising two and three strains, respectively) shared identical genome sequences, suggesting the possibility of limited human-to-human transmission. In contrast, the remaining 18 G4P[6] strains were genetically distinct from one another, indicating multiple, independent interspecies transmission events from pigs to humans. Phylogenetic analysis revealed that the P[6] genome segments of porcine RVA or porcine-like human RVA strains, including those identified in this study, were genetically distinct from those of typical human RVA strains and showed notable geographic variation in detection frequency. Comparative analysis of the variable regions of P[6] amino acid sequences identified characteristic residues that distinguish porcine RVA-like P[6] from human RVA-like P[6], some of which correspond to known glycan-binding sites. This study revealed a high frequency of pig-to-human spillover transmission of porcine-derived G4P[6] rotavirus strains in Vietnamese children. The findings suggest that these cases were not the result of newly emerging strains capable of sustained human-to-human transmission. Furthermore, distinct amino acid characteristics in the porcine RVA P[6] protein were identified that may play a role in facilitating the cross-species transmission of rotavirus from pigs to humans.