There are two ways in which murine norovirus infection may not represent the same biology as HuNV infection. The first is the lack of diarrhea in mice infected with the strains of MNV used here. It is possible that the adaptive responses that clear MNV from the intestine demonstrated here are irrelevant to the responses that may prevent human disease. In this regard, it is important to note that studies of adult mice with rotaviruses (also an infection only model), have been important to our consider-ations of rotavirus vaccines [57] . Importantly, human studies may not reveal the mechanisms of effective immunity and are based on surrogate assays of immunity, since invasive sampling of tissues may be technically difficult. Studies in piglets may be revealing since piglets develop diarrhea when infected with the HuNV strain, HuNoV-HS66 [37] . However, it is more difficult to study immune mechanisms in this system. Thus, we are left with several imperfect systems for considering what one should seek in a HuNV vaccine. Our studies in mice argue for a vaccine that induces all aspects of the adaptive immune response, and that assays for cytotoxic lymphocyte responses to HuNV infection may be an important surrogate assay for protection.