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Novel rat models to study primary genital herpes simplex virus-2 infection

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Abstract

In this study we describe that six rat models (SD, WIST, LEW, BN, F344 and DA) are susceptible to intravaginal herpes simplex virus-2 (HSV-2) infection after pre-treatment with progesterone. At a virus dose of 5 × 106 PFU of HSV-2, all rat models were infected presenting anti-HSV-2 antibodies, infectious virus in vaginal washes, and HSV-2 DNA genome copies in lumbosacral dorsal root ganglia and the spinal cord. Most of the LEW, BN, F344, and DA rats succumbed in systemic progressive symptoms at day 8-14 post infection, but presented no or mild genital inflammation while SD and WIST rats were mostly infected asymptomatically. Infected SD rats did not reactivate HSV-2 spontaneously or after cortisone treatment. In an HSV-2 virus dose reduction study, F344 rats were shown to be most susceptible. We also investigated whether an attenuated HSV-1 strain (KOS321) given intravaginally, could protect from a subsequent HSV-2 infection. All LEW, BN, and F344 rats survived a primary HSV-1 infection and no neuronal infection was established. In BN and F344 rats, anti-HSV-1 antibodies were readily detected while LEW rats were seronegative. In contrast to naïve LEW, BN, and F344 rats where only 3 of 18 animals survived 5 × 106 PFU of HSV-2, 23 of 25 previously HSV-1 infected rats survived a challenge with HSV-2. The described models provide a new approach to investigate protective effects of anti-viral microbicides and vaccine candidates, as well as to study asymptomatic primary genital HSV-2 infection.

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Acknowledgements

This work was supported by grants from the ALF Foundation at Sahlgrenska University Hospital, the Gothenburg Medical Society (GLS), the Adlerbertska Foundation, the Clas Groschinsky Foundation, the Medical Research Council and Torsten Söderbergs Foundation. We thank Carolina Gustafsson for technical assistance.

Conflict of interest

None declared.

Ethical standard

This study was carried out in accordance to the rules stated by the Swedish board of agriculture. All animal experiments were approved by the ethical board in Gothenburg (Dnr 171-2013).

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Authors and Affiliations

  1. Section of Virology, Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    Karin Önnheim, Maria Ekblad, Staffan Görander, Tomas Bergström & Jan-Åke Liljeqvist

  2. Section of Bacteriology, Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    Stefan Lange

  3. Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    Eva Jennische

  4. Harlan Laboratories, 8520 Allison Pointe Boulevard, Suite 400, Indianapolis, IN, 46250, USA

    Sheryl Wildt

Authors
  1. Karin Önnheim
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  2. Maria Ekblad
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  4. Stefan Lange
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  8. Jan-Åke Liljeqvist
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Correspondence to Jan-Åke Liljeqvist.

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Önnheim, K., Ekblad, M., Görander, S. et al. Novel rat models to study primary genital herpes simplex virus-2 infection. Arch Virol 160, 1153–1161 (2015). https://doi.org/10.1007/s00705-015-2365-7

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  • DOI: https://doi.org/10.1007/s00705-015-2365-7

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