Serotype diversity and reassortment between human and animal rotavirus strains: implications for rotavirus vaccine programs.

The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1-G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A[6]) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.

Wild-type levels of Spo11-induced DSBs are required for normal single-strand resection during meiosis.

We have studied the repair of a DNA-DSB created by the VMA1-derived endonuclease in mutants that have different levels of Spo11-DSBs: WT (sae2), few (hop1), and none (spo11-Y135F). In spo11-Y135F and hop1 cells, intrachromosomal repair is more frequent than in WT and sae2 cells. In spo11-Y135F cells there was no chromosome pairing or synapsis and a faster turnover of resected DNA. Compared to WT and sae2 cells, spo11-Y135F and hop1 cells have a greater proportion of long resection tracts. The data suggest that high levels of Spo11-DSBs are required for normal regulation of resection, even at a DSB created by another protein. WT control over resection could be important for directing repair to be interchromosomal, increasing the chance of creating interhomolog connections essential to meiotic segregation.