Evolution and diversity in human herpes simplex virus genomes

Moriah L. Szpara, Derek Gatherer, Alejandro Ochoa, Benjamin Greenbaum, Aidan Dolan, Rory J. Bowden, Lynn W. Enquist, Matthieu Legendre, Andrew J. Davison

Research output: Contribution to journalArticlepeer-review

159 Scopus citations


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 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 the 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. Wealso 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.

Original languageEnglish (US)
Pages (from-to)1209-1227
Number of pages19
JournalJournal of virology
Issue number2
StatePublished - Jan 2014

All Science Journal Classification (ASJC) codes

  • Insect Science
  • Virology
  • Microbiology
  • Immunology


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