CRISPR-Cas9 system-driven site-specific selection pressure on Herpes simplex virus genomes

Virus Res. 2018 Jan 15:244:286-295. doi: 10.1016/j.virusres.2017.03.010. Epub 2017 Mar 6.

Abstract

The CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9) system has been widely used for viral genome editing, transcription regulation and chromosomal localization in eukaryotic cells. In this study, a guide RNA (gRNA) that specifically recognizes HSV-1 viral genomes was used in the CRISPR-Cas9 system to inhibit viral replication. This inhibition could be achieved with both wild type Cas9 protein and Cas9 nickase (D10A). By targeting viral genomes containing sequences recognized by the gRNA, the CRISPR-Cas9 system distinguished between different viral genome sequences and provided single nucleotide-specific selection pressure to significantly change the proportions of viruses in a mixed viral pool. This finding indicates the utility of this tool for virus selection without the need for antibiotics or reporter genes, which could potentially save time compared to other methods used for screening and purifying mutant viruses.

Keywords: CRISPR-Cas9; HSV-1; Selection pressure; Site-specific mutation; Viral genome replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • CRISPR-Associated Protein 9
  • CRISPR-Cas Systems*
  • Chlorocebus aethiops
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Deoxyribonuclease I / genetics
  • Deoxyribonuclease I / metabolism
  • Endonucleases / genetics*
  • Endonucleases / metabolism
  • Gene Editing / methods*
  • Genes, Reporter
  • Genome, Viral*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Herpesvirus 1, Human / genetics*
  • Herpesvirus 1, Human / metabolism
  • Homologous Recombination
  • Humans
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • RNA, Guide, CRISPR-Cas Systems / genetics*
  • RNA, Guide, CRISPR-Cas Systems / metabolism
  • Selection, Genetic
  • Vero Cells
  • Virus Replication

Substances

  • Bacterial Proteins
  • RNA, Guide, CRISPR-Cas Systems
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • CRISPR-Associated Protein 9
  • Cas9 endonuclease Streptococcus pyogenes
  • Endonucleases
  • Deoxyribonuclease I