PATHOGENESIS OF AN ATTENUATED AND A VIRULENT-STRAIN OF GROUP-A HUMAN ROTAVIRUS IN NEONATAL GNOTOBIOTIC PIGS

Gnotobiotic (Gn) pigs were orally inoculated with Wa strain (G1P1A[P8] ) human rotavirus (Wa HRV) serially passaged in Gn pigs (virulent) or cell culture (attenuated) to determine the median virus infectious dos e (ID50) and to assess the site of infection and type and progression of morphological lesions and clinical responses induced by these two s trains in Gn pigs. The ID50 of virulent Wa HRV was less than or equal to 1 f.f.u. whereas the infectivity of attenuated Wa HRV had to be det ermined by seroconversion and was similar to 1.3 x 10(6) f.f.u. Diarrh oea developed at 13 h postinoculation (p.i.) in pigs inoculated with s imilar to 10(5) f.f.u. of virulent Wa HRV and correlated with the pres ence of viral antigen within villous epithelial cells; villous atrophy developed later at 24 h p.i. and correlated with peak faecal viral ti tres; recovery from disease correlated with the return of morphologica lly normal villi. Virus, diarrhoea and villous atrophy were not detect ed in pigs inoculated with similar to 2 x 10(8) f.f.u. attenuated Wa H RV although HRV-specific serum antibodies were present by 7 days p.i. These findings demonstrate that virulent Wa HRV infection in Gn pigs o ccurs primarily within intestinal villous epithelial cells with villou s atrophy developing as a sequela to infection. However, factors other than villous atrophy appear to contribute to the early stages of HRV- associated disease expression in Gn pigs. The ability of the attenuate d virus to elicit virus-neutralizing serum antibodies without disease or pathology indicates promise in the use of such strains for oral imm unization.