title: Novel rat models to study primary genital herpes simplex virus-2 infection.
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 × 10(6) 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 × 10(6) 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.
authors.affiliation: Section of Virology, Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, karin.onnheim@gu.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Önnheim
authors.forename: Maria
authors.initials: M
authors.lastname: Ekblad
authors.forename: Staffan
authors.initials: S
authors.lastname: Görander
authors.forename: Stefan
authors.initials: S
authors.lastname: Lange
authors.forename: Eva
authors.initials: E
authors.lastname: Jennische
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergström
authors.forename: Sheryl
authors.initials: S
authors.lastname: Wildt
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Liljeqvist
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006558:Herpes Genitalis / Q000473:pathology* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000254:growth & development*; D018258:Herpesvirus 2, Human / Q000254:growth & development*; D051381:Rats; D016019:Survival Analysis; D014621:Vagina / Q000821:virology
chemical_list: D000914:Antibodies, Viral