Rapid generation of rotavirus single-gene reassortants by means of eleven plasmid-only based reverse genetics

J Gen Virol. 2020 Aug;101(8):806-815. doi: 10.1099/jgv.0.001443. Epub 2020 Jun 3.

Abstract

Reassortment is an important mechanism in the evolution of group A rotaviruses (RVAs), yielding viruses with novel genetic and phenotypic traits. The classical methods for generating RVA reassortants with the desired genetic combinations are laborious and time-consuming because of the screening and selection processes required to isolate a desired reassortant. Taking advantage of a recently developed RVA reverse genetics system based on just 11 cloned cDNAs encoding the RVA genome (11 plasmid-only system), we prepared a panel of simian SA11-L2 virus-based single-gene reassortants, each containing 1 segment derived from human KU virus of the G1P[8] genotype. It was shown that there was no gene-specific restriction of the reassortment potential. In addition to these 11 single-gene reassortants, a triple-gene reassortant with KU-derived core-encoding VP1-3 gene segments with the SA11-L2 genetic background, which make up a virion composed of the KU-based core, and SA11-L2-based intermediate and outer layers, could also be prepared with the 11 plasmid-only system. Finally, for possible clinical application of this system, we generated a series of VP7 reassortants representing all the major human RVA G genotypes (G1-4, G9 and G12) efficiently. The preparation of each of these single-gene reassortants was achieved within just 2 weeks. Our results demonstrate that the 11 plasmid-only system allows the rapid and reliable generation of RVA single-gene reassortants, which will be useful for basic research and clinical applications.

Keywords: 11 plasmid-only system; G genotypes; group A rotavirus; reassortment; reverse genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsid Proteins / genetics
  • Cell Line
  • Cricetinae
  • DNA, Complementary / genetics
  • Genome, Viral / genetics*
  • Genotype
  • Haplorhini
  • Humans
  • Plasmids / genetics*
  • RNA, Viral / genetics
  • Reassortant Viruses / genetics*
  • Recombination, Genetic / genetics
  • Reverse Genetics / methods
  • Rotavirus / genetics*
  • Rotavirus Infections / virology
  • Swine

Substances

  • Capsid Proteins
  • DNA, Complementary
  • RNA, Viral