Attenuated phenotypes and analysis of a herpes simplex virus 1 strain with partial deletion of the UL7, UL41 and LAT genes

Virol Sin. 2017 Oct;32(5):404-414. doi: 10.1007/s12250-017-3947-1. Epub 2017 Sep 29.

Abstract

We previously constructed a herpes simplex virus 1 (HSV-1) UL7 mutant virus (M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mutant, we further modified the UL41 gene, which encodes another tegument protein, and the latency-associated transcript (LAT) gene. Observations of the resulting mutants with modified UL7 and UL41 (M2) or UL7, UL41 and LAT (M3) genes indicated attenuated phenotypes, with lower proliferative ratios in various cells, non-lethal infections in mice and lower viral loads in nervous tissues compared with the wild-type strain. Furthermore, no LAT stable intron could be detected in the trigeminal ganglion of M3-infected animals. The results obtained with the three HSV-1 mutants indicate that the M3 mutant is an attenuated strain with low pathogenicity during both acute and latent infections. Together, the results support the use of the M3 mutant as a candidate for the development of an HSV-1 vaccine.

Keywords: LAT; UL41; UL7; herpes simplex virus 1 (HSV-1); mutant.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics
  • HEK293 Cells
  • Herpesvirus 1, Human / genetics*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Introns / genetics
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mutation / genetics
  • Nerve Tissue / metabolism
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trigeminal Ganglion / metabolism
  • Viral Matrix Proteins / genetics*
  • Viral Matrix Proteins / metabolism*
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • LAT protein, human
  • Membrane Proteins
  • UL7 protein, human herpesvirus 1
  • Ul41 protein, Human herpesvirus 1
  • Viral Matrix Proteins
  • Viral Proteins