Abstract

Evolution and Diversity in Human Herpes Simplex Virus Genomes.

Journal of Virology 88, no. 2 (January 2014): 1209–27. https://doi.org/10.1128/JVI.01987-13.

Herpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a common gene deletion and one-third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms; although protein sequence identity between strains exceeds 90% on average. In the first genome-scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments, and will aid in the selection of vaccine antigens that are invariant worldwide.

Authors

Moriah L. Szpara1,*, Derek Gatherer2, Alejandro Ochoa3, Benjamin Greenbaum5, Aidan Dolan2, Rory J. Bowden6, Lynn W. Enquist3,4, Matthieu Legendre7, Andrew J. Davison2

* Corresponding author

  1. Department of Biochemistry and Molecular Biology, and the Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA
  2. Division of Biomedical & Life Sciences, Lancaster University, Lancaster LA1 4YQ, UK
  3. Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA
  4. Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA
  5. Departments of Medicine, Division of Hematology and Medical Pathology; and The Tisch Cancer Institute, Icahn School of Medicine, Mount Sinai, New York, New York 10029, USA
  6. Department of Statistics, University of Oxford, Oxford OX1 3TG, UK
  7. CNRS, Aix-Marseille Université, IGS UMR7256, Marseille, France