c Rotavirus (RV) is the major etiological agent of acute gastroenteritis in infants worldwide. Although high-pressure processing (HPP) is a popular method to inactivate enteric pathogens in food, the sensitivity of different virus strains within same species and serotype to HPP is variable. This study aimed to compare the barosensitivities of seven RV strains derived from four serotypes (serotype G1, strains Wa, Ku, and K8; serotype G2, strain S2; serotype G3, strains SA-11 and YO; and serotype G4, strain ST3) following high-pressure treatment. RV strains showed various responses to HPP based on the initial temperature and had different inactivation profiles. Ku, K8, S2, SA-11, YO, and ST3 showed enhanced inactivation at 4°C compared to 20°C. In contrast, strain Wa was not significantly impacted by the initial treatment temperature. Within serotype G1, strain Wa was significantly (P < 0.05) more resistant to HPP than strains Ku and K8. Overall, the resistance of the human RV strains to HPP at 4°C can be ranked as Wa > Ku ؍ K8 > S2 > YO > ST3, and in terms of serotype the ranking is G1 > G2 > G3 > G4. In addition, pressure treatment of 400 MPa for 2 min was sufficient to eliminate the Wa strain, the most pressure-resistant RV, from oyster tissues. HPP disrupted virion structure but did not degrade viral protein or RNA, providing insight into the mechanism of viral inactivation by HPP. In conclusion, HPP is capable of inactivating RV at commercially acceptable pressures, and the efficacy of inactivation is strain dependent. R otavirus (RV) is the major etiological agent of acute gastroenteritis in infants worldwide (1, 2). RVs are estimated to cause nearly 500,000 deaths annually among children (3, 4). The virus is transmitted by the fecal-oral route, and contaminated water and food are common vehicles for infections (1,5,6). RV belongs to the genus Rotavirus, subfamily Sedoreovirinae, and family Reoviridae. There are eight species (groups) of rotavirus, referred to as A, B, C, D, E, F, G, and H. Humans are infected primarily by species A, B, and C, most commonly by species A. Rotavirus species A can be further divided into different serotypes. RV is a segmented double-stranded RNA virus with a triple-layer icosahedral capsid. The outer capsid glycoprotein (VP7) and the spike protein (VP4) differentiate RVs into 14 G (glycoprotein) serotypes and 27 different P (protease sensitivity) genotypes (1, 3, 4). Currently, five serotypes (G1 to G4 and G9) are the predominant circulating viruses, accounting for almost 95% of strains worldwide (1). Recently, commercial RV vaccines have been used in children to provide immunity against the most commonly circulating strains (4). Despite major efforts, RV outbreaks still occur worldwide due to the high genetic diversity of RVs and lack of cross-protection (2, 7-9). Therefore, alternative strategies for the prevention of RV infection must be established.Enteric viruses are a leading cause of foodborne illnesses. Within foodborne viruses, human norovirus (NoV), rotaviruses (RVs...