Norovirus is a major cause of acute gastroenteritis in humans. A norovirus outbreak occurred in Ohio in January 2010. Stool and saliva samples were obtained from six infected individuals. The full-length genomes of two representative strains (HS206 and HS210) were characterized. They belonged to GII.12 in the capsid but GII.g in the RNA polymerase region. Interestingly, an immunocompetent 2-year-old male shed virus for up to 30 days, as detected by real-time reverse transcription (RT)-PCR. Histo-blood group antigen (HBGA) typing of saliva showed that the norovirus strains infected various types of secretor-positive individuals (types A, B, and O). The viruslike particles of strain HS206 did not bind substantially to A/B/O antigens by synthetic HBGA binding, hemagglutination, or saliva binding assays. These results suggest that infection by this strain may not be A/B/O antigen dependent or that in vitro binding patterns do not always accurately reflect in vivo HBGA usage. This is different from the HBGA binding pattern of the previously reported GII.12/Aichi76 strain. Structural analysis of the predicted capsid of these GII.12 strains revealed two amino acid mismatches located near the HBGA binding sites. Four gnotobiotic pigs were inoculated orally with HS206 (6 × 10(10) genomic equivalents [GE]/pig). Virus shedding began at postinoculation days (PID) 1 to 3 and continued up to PID 16 (1 × 10(5) to 2 × 10(7) GE/ml). Gastroenteritis cases caused by GII.12 noroviruses have been recently reported worldwide. We observed that this emerging GII.12 norovirus infected humans regardless of A/B/O blood type. The infection of pigs by strain HS206 suggests that interspecies transmission of this strain is possible under experimental conditions.