Emergence of Equine-like G3P[8] Rotavirus Strains Infecting Children in Venezuela

<i>Rotavirus alphagastroenteritidis</i> is the leading cause of acute gastroenteritis worldwide in young humans and animals. In 2023-2024, a relatively high rotavirus detection rate (34.5%) was detected in children with diarrhea in Caracas. All rotavirus strains were typed as P[8], using a multiplex RT-PCR assay, while the G-type was not identified. This unusual pattern, not previously observed in Venezuela, prompted the VP7 gene sequencing of nineteen strains, which displayed a high sequence identity (99.3-100%) compatible with the G3 genotype. These strains clustered into a well-supported lineage IX encompassing human reassortants of equine-like G3P[8] strains described elsewhere, showing a very close genetic relationship (99.0-99.9%). Old G3 rotavirus isolates obtained from diarrheic samples in the past were included in the analysis and grouped into lineage I together with ancestral reference G3 strains. The novel G3P[8]s carry amino acid changes in VP7-neutralizing epitopes, compared with the RotaTeq-WI78-8-vaccine strain. Full genome sequencing of a representative strain revealed a genotype constellation including an equine-like G3P[8] in a DS-1-like backbone (I2-R2-C2-M2-A2-N2-T2-E2-H2), confirming the role of animal strains as a source of diversification, and the importance of unceasingly revising molecular typing strategies and vaccine efficacy to guarantee their success.