Viviana Parreño, Instituto Nacional de Tecnologia Agropecuaria

Chandika Gamage1, William Holl1,2, Viviana Parreño3,4, Côme J. Thieulent1, Udeni B. R. Balasuriya1, M. Aldana Vissani3,4,5, Maria E. Barrandeguy6, Mariano Carossino1,2 1Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA 2Louisiana Animal Disease Diagnostic Laboratory, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA 3Instituto de Virología, CICVyA, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires B1686, Argentina 4Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1425, Argentina 5Escuela de Veterinaria, Universidad del Salvador, Buenos Aires B1630, Argentina 6Plataforma de Salud Animal, Instituto Nacional de Investigación Agropecuaria (INIA), La Estanzuela, Semillero, Uruguay

Pathogenesis and Immunity

Rotavirus A (RVA) infections are a leading cause of diarrhea in foals. Suckling mice could serve as a useful tool to study the pathogenesis of equine RVA (ERVA) as well as a pre-clinical model for vaccine efficacy studies. This study aimed to comparatively evaluate the clinical, virological, and pathological features of equine RVA G3P[12] and G14P[12] infection in suckling mice and compare it with porcine OSU G5P[7] and bovine UK G6P[5] RVA strains. Following oral inoculation, neonatal mice developed short-lived diarrhea, with rates of 61% and 88% for ERVA G14P[12] and G3P[12], respectively. Viral replication kinetics for all strains were characterized by a gradual decline in viral load to levels below the limit of detection by 72-96 hours post-infection (hpi), in line with the reduction in the number of infected enterocytes demonstrated via VP6-specific RNAscope® in situ hybridization. Importantly, the clinical and viral replication kinetics correlated with significant microscopic intestinal alterations characterized by enterocyte vacuolation, scalloping, and hyperplasia with a peak occurring at 48 hpi and persisting until at least 96 hpi. Overall, neonatal mice developed a disease phenotype of short duration following infection with equine RVA strains and similar to porcine and bovine RVA reference strains, characterized by diarrhea and pronounced intestinal histologic alterations. The limited intestinal viral replication is attributed to host restriction. The clinical and pathological phenotypes developed by neonatal mice could serve as a preclinical tool to assess vaccine efficacy and for pathogenesis studies involving RVA of equine, porcine and bovine origin.