PMID- 25701211 OWN - NLM STAT- MEDLINE DCOM- 20150615 LR - 20150413 IS - 1432-8798 (Electronic) IS - 0304-8608 (Linking) VI - 160 IP - 5 DP - 2015 May TI - Novel rat models to study primary genital herpes simplex virus-2 infection. PG - 1153-61 LID - 10.1007/s00705-015-2365-7 [doi] AB - 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 x 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 naive LEW, BN, and F344 rats where only 3 of 18 animals survived 5 x 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. FAU - Onnheim, Karin AU - Onnheim K AD - Section of Virology, Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, karin.onnheim@gu.se. FAU - Ekblad, Maria AU - Ekblad M FAU - Gorander, Staffan AU - Gorander S FAU - Lange, Stefan AU - Lange S FAU - Jennische, Eva AU - Jennische E FAU - Bergstrom, Tomas AU - Bergstrom T FAU - Wildt, Sheryl AU - Wildt S FAU - Liljeqvist, Jan-Ake AU - Liljeqvist JA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150221 PL - Austria TA - Arch Virol JT - Archives of virology JID - 7506870 RN - 0 (Antibodies, Viral) SB - IM MH - Animals MH - Antibodies, Viral/blood MH - *Disease Models, Animal MH - Female MH - Herpes Genitalis/*pathology/*virology MH - Herpesvirus 1, Human/*growth & development MH - Herpesvirus 2, Human/*growth & development MH - Rats MH - Survival Analysis MH - Vagina/virology EDAT- 2015/02/24 06:00 MHDA- 2015/06/16 06:00 CRDT- 2015/02/22 06:00 PHST- 2014/10/03 00:00 [received] PHST- 2015/02/09 00:00 [accepted] PHST- 2015/02/22 06:00 [entrez] PHST- 2015/02/24 06:00 [pubmed] PHST- 2015/06/16 06:00 [medline] AID - 10.1007/s00705-015-2365-7 [doi] PST - ppublish SO - Arch Virol. 2015 May;160(5):1153-61. doi: 10.1007/s00705-015-2365-7. Epub 2015 Feb 21.