Genetic diversity and classification of human and animal rotaviruses.

Rotavirus infections cause more than 600.000 deaths in children each year. Rotaviruses have a segmented genome consisting of 11 segments of double-stranded RNA encoding 6 structural (VP) and 6 non-structural (NSP) proteins. VP7 and VP4 form the outer capsid of the rotavirus and are used for a dual classification system defining respectively G and P-genotypes. Currently, the most common human rotavirus genotypes worldwide are G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. The G9 VP7-genotype has only emerged recently, and is believed to have a porcine ancestor. Rotaviruses use a number of different strategies to generate genetic diversity and to adapt to changing environments. The most common mechanism for viruses to change their genetic material is the accumulation of point mutations due to errors made by the replication machinery used by the virus. This "genetic drift" is a slow continuous process, resulting in offspring only slightly different from the parental virus. A second important mechanism that rotaviruses employ to generate genetic diversity is reassortment. Reassortment is a natural process and it is a property only viruses with a segmented genome, such as rotaviruses or influenze viruses, can use. Reassortments can occur when two viruses infect the same well and new progeny viruses may be assembled possessing a number of genes and phenotypic properties of both parental strains. Since reassortment events result in sudden drastic hanges into the rotavirus genome, it is also referred to as "genetic shift". The reassortment process most often occurs between different rotavirus strains circulating in the same species, but it can also occur between rotaviruses from two different species, after one of the viruses infects another host across the species barrier. It is unknown how frequent rotaviruses cross the species barrier, as in most cases this will lead to an asymptomatic death-end infection, which remains undetected. However, when these interspecies-transmitted viruses manage to reassort with a rotavirus strain endemic in that species, it has a much greater chance of becoming established in the new species. It is currently believed that this mechanism was used by the porcine G9 genotype to become established in the human population. Two other minor mechanisms causing genetic shifts in the rotavirus genome are rearrangement and recombination. Rearrangement can cause deletions, insertions and (partial) duplications into rotavirus genes, and especially partial duplications have been described on multiple occasions for rotaviruses. Recombination between cognate genes of different rotaviruses may result in a strain with a mosaic gene derived from the two parental strains. The goal of this thesis was to study the genetic diversity of rotaviruses and the mechanisms employed by rotaviruses to generate this genetic diversity. Our lab has been one of the pioneers in sequencing and phylogenetic analyses of complete rotavirus genomes. In the past, only a limited number of the rotavirus gene segments were analysed, or rotavirus genomes wherecompared to each other by RNA-RNA-hybridisation. Using these hybridisation assays, two major human genogroups, represented by the prototype strains Wa and DS-1, and one minor genogroup, represented by the prototype strain AU-1, have been established. However, sequencing of complete genomes has become the standard for the complete molecular characterization of rotavirus strains. Due to the accumulating sequence data of complete rotavirus genomes, a proper way to classify all the 11 gene segments became a necessity.

Keywords:Rotaviruses, Epidemiology, Classification, Reassortment, Gastroenteritis

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences, Scientific computing, Bioinformatics and computational biology, Public health care, Public health services, Microbiology, Systems biology, Immunology