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Evolution and diversity in human herpes simplex virus genomes.

Moriah L Szpara1, Derek Gatherer, Alejandro Ochoa

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Herpes simplex virus 1 (HSV-1) diversity is significant, with gene deletions and frameshift mutations common. Understanding this variation is crucial for developing effective HSV-1 vaccines.

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Area of Science:

  • Virology
  • Genomics
  • Molecular Biology

Background:

  • Herpes simplex virus 1 (HSV-1) establishes chronic infections in over 60% of adults.
  • Recent HSV-1 vaccine trials have faced challenges, potentially due to viral diversity.
  • Understanding HSV-1 genetic variation is critical for vaccine development.

Purpose of the Study:

  • To comprehensively analyze the genetic diversity of HSV-1 strains from diverse geographic locations.
  • To identify common genetic variations, including gene deletions and homopolymeric frameshift mutations (HFMs).
  • To investigate patterns of positive selection and recombination within the HSV-1 genome.

Main Methods:

  • Sequencing of 20 new HSV-1 genomes from China, Japan, Kenya, and South Korea.
  • Comparative genomic analysis with six previously sequenced HSV-1 genomes.
  • Genome-scale analysis for positive selection and recombination events.

Main Results:

  • One-fifth of newly sequenced strains share a gene deletion; one-third exhibit HFMs.
  • Significant genotypic variation observed through HFMs, deletions, SSRs, and SNPs, with >90% average protein sequence identity.
  • Evidence of positive selection in specific proteins like glycoprotein H and high recombination frequency across the genome.
  • HSV-1 strains clustered by geographic origin despite extensive genetic variation.

Conclusions:

  • HSV-1 exhibits substantial genetic diversity, influenced by gene deletions, HFMs, and recombination.
  • Geographic origin is a significant factor in HSV-1 strain clustering.
  • Insights into HSV-1 adaptation and selection of invariant vaccine antigens are provided.