Rotaviruses and Rotavirus Vaccines

Rotaviruses were first described in 1963 when they were observed during electron microscopy of faecal samples from monkeys and mice. Some 10 years later, similar viruses with the characteristic spherical structure resembling the spokes of a wheel were observed in faecal samples from children with diarrhoea (Fig. 1). The capsid, a protein coat that surrounds the genome, has three layers each constructed from a different viral protein (VP). The inner and middle layers, constructed from VP2 and VP6, respectively, are perforated by channels. The middle layer contains the 'spokes' of the wheel and is a major constituent of the virion. The outer layer is constructed from another protein, VP7, which is a glycoprotein. Three other proteins are found in the virion, VP1 and VP3 in the core, and VP4 which forms 60 spikes on the surface (Fig. 2). Both VP7 and VP4 have a role in protective immunity. The proteins are numbered in order of their size, the largest being towards the centre of the virion. Associated with the genome within the inner capsid layer are copies of VP1 and VP3 which are enzymes (Fig. 3). The genome comprises 11 double stranded RNA segments. Each segment encodes one protein except one segment which encodes two proteins. Thus in all 12 proteins are encoded—six structural and six non-structural proteins. The two structural proteins that comprise the outer viral capsid are the neutralization antigens VP7 (or G for glycoprotein) and VP4 (or P for protease sensitive). They define the serotypes [1]. There are 23 P and 15 G serotypes. Five G–P combinations G1P8, G2P4, G3P8, G4P8 and G9P8 constitute 90% of human rotavirus strains worldwide. G1P8 strains are most prevalent but large regional differences exist and strain types can change with time [2]. This has implication in the development of vaccine. Change in serotypes occurs because of: (i) Point mutation (or 'drift'). (ii) Genomic reassortment caused by exchange of RNA segments between strains (or 'shift'). Overall most reassortment occurs in the genes encoding VP7 and VP4. (iii) Duplication and deletion of sequences within a segment. (iv) Introduction of animal rotaviruses into the human population. Reassortment and crossing of species barrier results in a large number of G types besides just the G1 and G4 in some regions. Thus serotypes G5, G8 and G9 have been described as important serotypes encountered in Brazil, Malawi, India and Bangladesh, respectively [2, 3]. The virion utilizes …