Murine norovirus-1 (MNV) is currently the most suitable surrogate for human norovirus. The mechanism of MNV-1 inactivation by high pressure processing (HPP) was investigated. HPP-treated MNV could not bind to its target receptor and therefore could not initiate infection of mouse RAW cells. The integrity of the capsid was not affect by HPP. Partial motif changes of the viral capsid caused by HPP were accessed by induced sensitivity to proteinase K.