Comparative In Vitro and In Vivo Studies of Porcine Rotavirus G9P and Human Rotavirus Wa G1P
Shao L, Fischer DD, Kandasamy S, Rauf A, Langel SN, Wentworth DE, Stucker KM, Halpin RA, Lam HC, Marthaler D, Saif LJ, Vlasova AN
The changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P induced only partial protection against PRV challenge. Moreover, PRV G9P replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes.