Molecular studies in rotavirus replication. (360G-Wellcome-080984_Z_06_Z)

Rotaviruses are a major cause of gastroenteritis in young children, leading to one hundred million rotavirus infections per annum worldwide, one quarter of all childhood diarrhoea hospitalisations, and over 600,000 deaths each year. There is an urgent need for an effective rotavirus vaccine. Recently, two live attenuated rotavirus vaccines have been found to be safe in large phase III clinical trials and have been licensed in various countries, in some cases for universal use in childhood vaccination programmes. Various aspects of the rotavirus replication cycle are still relatively poorly understood, and successful therapeutic approaches will require further investigation of rotavirus replication at a molecular level. Rotaviruses constitute a genus of the Reoviridae family. They possess a genome of 11 segments of double-stranded (ds) RNA, which encodes 6 structural (VP1-VP4, VP6, and VP7) and 6 non-structural proteins (NSP1-NSP6). The infectious article (=virion) is a non-enveloped icosahedron. The structural proteins are located in three layers, with the outer layer formed by VP4 and VP7, the intermediate layer by VP6, and the inner layer by VP1-VP3, and the particle structure is characterised by the wheel-like appearance as observed by electron microscopy. Rotaviruses have been classified according to the immunological reactivities and gene composition of VP6, the middle layer protein, defining at least 5 groups (A-E), with a further possible 2 groups (F-G). For group A rotaviruses, G and P types have been established for classification, according to the immunological reactivity and gene composition of VP7 and VP4, respectively.