Genome Sequencing and Analysis of Geographically Diverse Clinical Isolates of Herpes Simplex Virus 2.
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Abstract | UNLABELLED: 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. IMPORTANCE: 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. |
Year of Publication | 2015
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Journal | J Virol
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Volume | 89
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Issue | 16
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Pages | 8219-32
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Date Published | 2015 Aug
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ISSN | 1098-5514
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DOI | 10.1128/JVI.01303-15
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PubMed ID | 26018166
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PubMed Central ID | PMC4524243
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Grant list | R56 AI057552 / AI / NIAID NIH HHS / United States
HHSN272200900018C / AI / NIAID NIH HHS / United States
AI057552 / AI / NIAID NIH HHS / United States
R01 AI094019 / AI / NIAID NIH HHS / United States
P01 AI030731 / AI / NIAID NIH HHS / United States
R01 AI057552 / AI / NIAID NIH HHS / United States
AI030731 / AI / NIAID NIH HHS / United States
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