Norovirus (NoV) is the major causative agent of acute viral gastroenteritis worldwide. Based on genetic analyses, human NoV strains have been classified into at least three genogroups: genogroup I (GI), GII, and GIV, which contain at least 15, 18, and 1 genotypes, respectively (Kageyama et al., 2004). Notably, these NoV genotypes are morphologically similar to one another but differ antigenically (Kapikian, 1996; Estes et al., 1997; Hansman et al., 2006). Since no cell culture system has been developed yet, molecular analyses to elucidate the mechanisms underlying infection or productive replication have been stalled until recently. The primary NoV replication site in humans is unknown, but intestinal biopsy from volunteer who became ill following oral administration of NoV exhibited histopathologic lesions, in which the villi of the proximal small intestine were blunted (Agus et al., 1973). More than 30 years ago, the initial NoV challenge studies conducted in volunteers found that a subset of individuals was repeatedly susceptible to NoV infection, whereas a second subset was repeatedly resistant to infection (Parrino et al., 1977). A genetic factor, possibly a receptor, was hypothesized to affect the susceptibility of an individual to NoV infection. Recently, a mechanism that explains the susceptibility or resistance to NoV infection has been identified; namely, NoV attaches to histo-blood group antigens (HBGAs) on potential host cells in the gut (Lindesmith et al., 2003).