title: Genome Sequencing and Analysis of Geographically Diverse Clinical Isolates of Herpes Simplex Virus 2.
abstract: Herpes simplex virus 2 (HSV-2), the principal causative agent of recurrent genital herpes, is a highly prevalent viral infection worldwide. Limited information is available on the amount of genomic DNA variation between HSV-2 strains because only two genomes have been determined, the HG52 laboratory strain and the newly sequenced SD90e low-passage-number clinical isolate strain, each from a different geographical area. In this study, we report the nearly complete genome sequences of 34 HSV-2 low-passage-number and laboratory strains, 14 of which were collected in Uganda, 1 in South Africa, 11 in the United States, and 8 in Japan. Our analyses of these genomes demonstrated remarkable sequence conservation, regardless of geographic origin, with the maximum nucleotide divergence between strains being 0.4% across the genome. In contrast, prior studies indicated that HSV-1 genomes exhibit more sequence diversity, as well as geographical clustering. Additionally, unlike HSV-1, little viral recombination between HSV-2 strains could be substantiated. These results are interpreted in light of HSV-2 evolution, epidemiology, and pathogenesis. Finally, the newly generated sequences more closely resemble the low-passage-number SD90e than HG52, supporting the use of the former as the new reference genome of HSV-2.
  
  
  OBJECTIVE
  Herpes simplex virus 2 (HSV-2) is a causative agent of genital and neonatal herpes. Therefore, knowledge of its DNA genome and genetic variability is central to preventing and treating genital herpes. However, only two full-length HSV-2 genomes have been reported. In this study, we sequenced 34 additional HSV-2 low-passage-number and laboratory viral genomes and initiated analysis of the genetic diversity of HSV-2 strains from around the world. The analysis of these genomes will facilitate research aimed at vaccine development, diagnosis, and the evaluation of clinical manifestations and transmission of HSV-2. This information will also contribute to our understanding of HSV evolution.
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA rnewman4@mgh.harvard.edu.
authors.forename: Ruchi M
authors.initials: RM
authors.lastname: Newman
authors.affiliation: Bioinfoexperts, LLC, Thibodaux, Louisiana, USA.
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Lamers
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Weiner
authors.affiliation: Departments of Medicine and Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA Department of Medicine, Mount Auburn Hospital, Cambridge, Massachusetts, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Colgrove
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Diaz
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Lichen
authors.initials: L
authors.lastname: Jing
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kening
authors.initials: K
authors.lastname: Wang
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Sakina
authors.initials: S
authors.lastname: Saif
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Young
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Henn
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.affiliation: Departments of Medicine and Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Aaron A R
authors.initials: AA
authors.lastname: Tobian
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA Department of Laboratory Medicine and Global Health, University of Washington, Seattle, Washington, USA Vaccine and Infectious Diseases Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.affiliation: Departments of Medicine and Pathology, Johns Hopkins University, Baltimore, Maryland, USA Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
mesh_terms: D014644:Genetic Variation; D016679:Genome, Viral; D005843:Geography; D018258:Herpesvirus 2, Human / Q000145:classification / Q000235:genetics*; D006801:Humans; D011995:Recombination, Genetic