Live attenuated pseudorabies virus developed using the CRISPR/Cas9 system

Virus Res. 2016 Oct 2:225:33-39. doi: 10.1016/j.virusres.2016.09.004. Epub 2016 Sep 13.

Abstract

Currently, pseudorabies virus (PRV) variant strains are outbreaking in China; these variants belong to genotype II PRV. The traditional Bartha-K61 vaccine has failed to provide complete protection against the emergent variant strains. Therefore, rapid attenuation of current epidemic strains is needed for effective PRV control. In this study, we report a rapid method for editing the PRV genome using the CRISPR-Cas9 system. We developed a triple gE/gI/TK gene-inactivated HeN1 PRV strain, because mice were more susceptible to PRV infection, we then evaluated the attenuation of PRV in the mice and demonstrated that modified PRV was fully attenuated. Furthermore, the attenuated strain also induced immune protection in response to a parental PRV challenge. Overall, we showed that PRVs can be rapidly attenuated using CRISPR-Cas9 technology, which will be critical for PRV control, especially when new variant PRV strains emerge.

Keywords: Attenuation; CRISPR/Cas9; Pseudorabies virus; Vaccine.

MeSH terms

  • Animals
  • CRISPR-Cas Systems*
  • Chlorocebus aethiops
  • Female
  • Gene Editing
  • Gene Targeting
  • Genetic Vectors / genetics*
  • Herpesvirus 1, Suid / genetics*
  • Herpesvirus 1, Suid / immunology
  • Mice
  • Pseudorabies Vaccines / genetics*
  • Pseudorabies Vaccines / immunology
  • RNA, Guide, CRISPR-Cas Systems
  • Sequence Deletion
  • Vaccines, Attenuated / genetics*
  • Vaccines, Attenuated / immunology
  • Vero Cells
  • Virus Replication

Substances

  • Pseudorabies Vaccines
  • RNA, Guide, CRISPR-Cas Systems
  • Vaccines, Attenuated