The Belgian rotavirus strain B4106, isolated from a child with gastroenteritis, was previously found to have VP7 (G3), VP4 (P[14]), and NSP4 (A genotype) genes closely related to those of lapine rotaviruses, suggesting a possible lapine origin or natural reassortment of strain B4106. To investigate the origin of this unusual strain, the gene sequences encoding VP1, VP2, VP3, VP6, NSP1, NSP2, NSP3, and NSP5/6 were also determined. To allow comparison to a lapine strain, the 11 double-stranded RNA segments of a European G3P[14] rabbit rotavirus strain 30/96 were also determined. The complete genome similarity between strains B4106 and 30/96 was 93.4% at the nucleotide level and 96.9% at the amino acid level. All 11 genome segments of strain B4106 were closely related to those of lapine rotaviruses and clustered with the lapine strains in phylogenetic analyses. In addition, sequence analyses of the NSP5 gene of strain B4106 revealed that the altered electrophoretic mobility of NSP5, resulting in a super-short pattern, was due to a gene rearrangement (head-to-tail partial duplication, combined with two short insertions and a deletion). Altogether, these findings confirm that a rotavirus strain with an entirely lapine genome complement was able to infect and cause severe disease in a human child.Group A rotaviruses (family Reoviridae) are important enteropathogens of humans and of a large variety of mammals and birds (11, 37). The rotavirus genome consists of 11 segments of double-stranded RNA (dsRNA) encoding six structural viral proteins (VP) and six nonstructural proteins (NSP) (37). A mature infectious rotavirus particle is composed of three concentric layers, consisting of a protein core, an inner protein capsid, and an outer protein capsid (84). The outer protein layer consists of VP4 and VP7, the two independent neutralization antigens of the virus, defining 26 P (proteasesensitive) and 15 G (glycoprotein) types, respectively (37,55,68,69,85). The G and P types are peculiarly distributed across the various animal species (88), suggesting host species barriers and restriction, although a number of unusual G and P types, regarded as animal-like strains, have been identified in humans in different parts of the world (85, 88).Although rotaviruses infect particular species preferentially for which they have been defined as the homologous strains, heterologous rotavirus infections occur in both natural and experimental circumstances. Studies in the rabbit and mouse models have demonstrated that only homologous virus strains replicate efficiently and spread horizontally (21,38,44). Based on a Jennerian approach, animal strains that are naturally attenuated in humans have been exploited for the construction of candidate rotavirus vaccines for humans. In a number of field trials with such candidate rotavirus vaccines, the rhesus rotavirus (RRV) strain MMU18006 and the bovine strains NCDV, UK, and WC3 were shown to replicate to a lower extent in humans than in their homologous hosts but to induce immune responses (24, 2...