A 12-year molecular survey of clinical herpes simplex virus type 2 isolates demonstrates the circulation of clade A and B strains in Germany

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Abstract

Background

Recently two different herpes simplex virus type 2 (HSV-2) clades (A and B) were described on DNA sequence data of the glycoprotein E (gE), G (gG) and I (gI) genes.

Objective

To type the circulating HSV-2 wild-type strains in Germany by a novel approach and to monitor potential changes in the molecular epidemiology between 1997 and 2008.

Study design

A total of 64 clinical HSV-2 isolates were analyzed by a novel approach using the DNA sequences of the complete open reading frames of glycoprotein B (gB) and gG. Recombination analysis of the gB and gG gene sequences was performed to reveal intragenic recombinants.

Results

Based on the phylogenetic analysis of the gB coding DNA sequence 8 of 64 (12%) isolates were classified as clade A strains and 56 of 64 (88%) isolates were classified as clade B strains. Analysis of the gG coding DNA sequence classified 4 (6%) isolates as clade A strains and 60 (94%) isolates as clade B strains. In comparison, the 8 isolates classified as clade A strains using the gB sequence data were classified as clade B strains when using the gG coding DNA sequence, suggesting intergenic recombination events. Intragenic recombination events were not detected.

Conclusion

The first molecular survey of clinical HSV-2 isolates from Germany demonstrated the circulation of clade A and B strains and of intergenic recombinants over a period of 12 years.

Section snippets

Background

Herpes simplex virus type 2 (HSV-2, Human Herpesvirus 2) is a human representative of the subfamily Alphaherpesvirinae within the family Herpesviridae. After primary infection HSV-2 typically establishes latency in the sacral ganglia. HSV-2 reactivation from latency is the main cause of genital herpes worldwide and responsible for an increased risk of human immunodeficiency virus (HIV) acquisition in HIV-negative individuals.8 The HSV-2 genome is a 155 kb linear, double-stranded DNA molecule and

Objective

In contrast to the large number of seroepidemiological studies performed in Central Europe, no molecular epidemiological study on HSV-2 has been performed so far in Central Europe and in Germany in particular. Therefore, the objectives of our study in Germany were (i) to type the circulating HSV-2 wild-type strains by a novel approach and (ii) to monitor potential changes in the molecular epidemiology between 1997 and 2008.

Study design

Swabs were obtained between 1997 and 2008 from 64 herpes patients that were referred to the Hospital of the Johann Wolfgang Goethe University, Frankfurt am Main, Germany. Virus isolation was performed in Vero cells (ATCC CRL-1587, Rockville, MD) using the shell vial assay and subsequent staining with HSV-2-specific monoclonal antibodies (Argene/Biosoft, Varilhes, France) as described recently.3 If several isolates were available from a single patient only the first isolate was included in the

Results and discussion

The gB coding DNA sequence of HSV-2 was chosen as a novel target because it is one of the most highly conserved genes within the family Herpesviridae and previously successfully used for reliable phylogenetic analysis of novel reptilian and mammalian herpesviruses.5, 15 Based on the phylogenetic analysis of the gB coding DNA sequence by fast maximum-likelihood (ML) inference7 and Neighbor-net,10 8 of 64 (12%) isolates were classified as clade A strains and 56 of 64 (88%) isolates were

Conflict of interest

The authors do not have commercial or other associations that might pose a conflict of interest (e.g., pharmaceutical stock ownership or consultancy).

Acknowledgment

The work was supported by the Hospital of the Johann Wolfgang Goethe University.

References (20)

  • R. Gupta et al.

    Genital herpes

    Lancet

    (2007)
  • M. Padidam et al.

    Possible emergence of new geminiviruses by frequent recombination

    Virology

    (1999)
  • J. Schmidt-Chanasit et al.

    A 10-year molecular survey of herpes simplex virus type 1 in Germany demonstrates a stable and high prevalence of genotypes A and B

    J Clin Virol

    (2009)
  • M.F. Boni et al.

    An exact nonparametric method for inferring mosaic structure in sequence triplets

    Genetics

    (2007)
  • T.C. Bruen et al.

    A simple and robust statistical test for detecting the presence of recombination

    Genetics

    (2006)
  • S. Buxbaum et al.

    Epidemiology of herpes simplex virus types 1 and 2 in Germany: what has changed?

    Med Microbiol Immunol

    (2003)
  • A. Dolan et al.

    The genome sequence of herpes simplex virus type 2

    J Virol

    (1998)
  • B. Ehlers et al.

    Identification of novel rodent herpesviruses, including the first gammaherpesvirus of Mus musculus

    J Virol

    (2007)
  • M.J. Gibbs et al.

    Sister-Scanning: a Monte Carlo procedure for assessing signals in recombinant sequences

    Bioinformatics

    (2000)
  • S. Guindon et al.

    A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood

    Syst Biol

    (2003)
There are more references available in the full text version of this article.

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