HSV-1 clinical isolates with unique in vivo and in vitro phenotypes and insight into genomic differences

J Neurovirol. 2017 Apr;23(2):171-185. doi: 10.1007/s13365-016-0485-9. Epub 2016 Oct 13.


Strain-specific factors contribute in significant but undefined ways to the variable incidence of herpes simplex virus (HSV) recrudescence. Studies that investigate these strain-specific factors are needed. Here, we used qPCR, in vitro assays, and genomic sequencing to identify important relationships between in vitro and clinical phenotypes of unique HSV-1 clinical isolates. Nine HSV-1 isolates from individuals displaying varying reactivation patterns were studied. Isolates associated with frequent recurrent herpes labialis (RHL) (1) displayed higher rates of viral shedding in the oral cavity than those associated with rare RHL and (2) tended to replicate more efficiently at 33 °C than 39 °C. HSV-1 isolates also displayed a more stable phenotype during propagation in U2OS cells than in Vero cells. Draft genome sequences of four isolates and one variant spanning 95.6 to 97.2 % of the genome were achieved, and whole-genome alignment demonstrated that the majority of these isolates clustered with known North American/European isolates. These findings revealed procedures that could help identify unique genotypes and phenotypes associated with HSV-1 isolates, which can be important for determining viral factors critical for regulating HSV-1 reactivation.

Keywords: Genetic variation; Genome; Herpes virus 1; Human/isolation and purification; Phylogeny; Recurrence; Viral; Virus replication.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Female
  • Genome, Viral*
  • Genotype*
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / classification
  • Herpesvirus 1, Human / genetics*
  • Herpesvirus 1, Human / growth & development
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Osteoblasts / pathology
  • Osteoblasts / virology
  • Phenotype*
  • Phylogeny*
  • Polymorphism, Single Nucleotide*
  • Sequence Alignment
  • Vero Cells
  • Virus Activation