PMID- 26002839 OWN - NLM STAT- MEDLINE DCOM- 20160824 LR - 20181113 IS - 1538-2443 (Electronic) IS - 1355-0284 (Print) IS - 1355-0284 (Linking) VI - 21 IP - 5 DP - 2015 Oct TI - Decreased reactivation of a herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) mutant using the in vivo mouse UV-B model of induced reactivation. PG - 508-17 LID - 10.1007/s13365-015-0348-9 [doi] AB - Blinding ocular herpetic disease in humans is due to herpes simplex virus type 1 (HSV-1) reactivations from latency, rather than to primary acute infection. The cellular and molecular immune mechanisms that control the HSV-1 latency-reactivation cycle remain to be fully elucidated. The aim of this study was to determine if reactivation of the HSV-1 latency-associated transcript (LAT) deletion mutant (dLAT2903) was impaired in this model, as it is in the rabbit model of induced and spontaneous reactivation and in the trigeminal ganglia (TG) explant-induced reactivation model in mice. The eyes of mice latently infected with wild-type HSV-1 strain McKrae (LAT((+)) virus) or dLAT2903 (LAT((-)) virus) were irradiated with UV-B, and reactivation was determined. We found that compared to LAT((-)) virus, LAT((+)) virus reactivated at a higher rate as determined by shedding of virus in tears on days 3 to 7 after UV-B treatment. Thus, the UV-B-induced reactivation mouse model of HSV-1 appears to be a useful small animal model for studying the mechanisms involved in how LAT enhances the HSV-1 reactivation phenotype. The utility of the model for investigating the immune evasion mechanisms regulating the HSV-1 latency/reactivation cycle and for testing the protective efficacy of candidate therapeutic vaccines and drugs is discussed. FAU - BenMohamed, Lbachir AU - BenMohamed L AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. Lbenmoha@uci.edu. AD - Department of Molecular Biology & Biochemistry, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. Lbenmoha@uci.edu. AD - Institute for Immunology, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. Lbenmoha@uci.edu. AD - Laboratory of Cellular and Molecular Immunology, Ophthalmology Research Laboratories, Gavin Herbert Eye Institute, Hewitt Hall (Building 843), Room 2032, Irvine, CA, 92697, USA. Lbenmoha@uci.edu. FAU - Osorio, Nelson AU - Osorio N AD - Virology Research, Gavin Herbert Eye Institute and Department of Ophthalmology, School of Medicine, University of California Irvine, 843 Health Sciences Road, Hewitt Hall (Building 843), Room 2012, Irvine, CA, 92697, USA. FAU - Srivastava, Ruchi AU - Srivastava R AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. FAU - Khan, Arif A AU - Khan AA AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. FAU - Simpson, Jennifer L AU - Simpson JL AD - Gavin Herbert Eye Institute and Department of Ophthalmology, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. FAU - Wechsler, Steven L AU - Wechsler SL AD - Virology Research, Gavin Herbert Eye Institute and Department of Ophthalmology, School of Medicine, University of California Irvine, 843 Health Sciences Road, Hewitt Hall (Building 843), Room 2012, Irvine, CA, 92697, USA. Wechsler@uci.edu. AD - Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. Wechsler@uci.edu. AD - Center for Virus Research, University of California Irvine, Irvine, CA, 92697, USA. Wechsler@uci.edu. LA - eng GR - R56 AI098985/AI/NIAID NIH HHS/United States GR - R01 EY013191/EY/NEI NIH HHS/United States GR - R01EY024618/EY/NEI NIH HHS/United States GR - R56 AI093133/AI/NIAID NIH HHS/United States GR - R01 EY019896/EY/NEI NIH HHS/United States GR - R01 EY022365/EY/NEI NIH HHS/United States GR - R01EY14900/EY/NEI NIH HHS/United States GR - R01EY019896/EY/NEI NIH HHS/United States GR - R01EY013191/EY/NEI NIH HHS/United States GR - R01EY022365/EY/NEI NIH HHS/United States GR - 1R56AI098985/AI/NIAID NIH HHS/United States GR - R01 EY014900/EY/NEI NIH HHS/United States GR - 1R56AI093133/AI/NIAID NIH HHS/United States GR - R01 EY024618/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150522 PL - United States TA - J Neurovirol JT - Journal of neurovirology JID - 9508123 RN - 0 (MicroRNAs) RN - 0 (latency associated transcript, herpes simplex virus-1) SB - IM MH - Animals MH - Disease Models, Animal MH - Female MH - Herpesvirus 1, Human/*physiology MH - Keratitis, Herpetic/*virology MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics MH - Ultraviolet Rays MH - Virus Activation/*genetics MH - Virus Latency/*genetics PMC - PMC4618093 MID - NIHMS693978 OTO - NOTNLM OT - Animal model OT - Eye OT - HSV-1 OT - Immunology OT - LAT OT - Recurrent herpetic disease OT - UV-B OT - Virology EDAT- 2015/05/24 06:00 MHDA- 2016/08/25 06:00 PMCR- 2016/10/01 CRDT- 2015/05/24 06:00 PHST- 2015/03/10 00:00 [received] PHST- 2015/04/22 00:00 [accepted] PHST- 2015/04/15 00:00 [revised] PHST- 2015/05/24 06:00 [entrez] PHST- 2015/05/24 06:00 [pubmed] PHST- 2016/08/25 06:00 [medline] PHST- 2016/10/01 00:00 [pmc-release] AID - 10.1007/s13365-015-0348-9 [pii] AID - 10.1007/s13365-015-0348-9 [doi] PST - ppublish SO - J Neurovirol. 2015 Oct;21(5):508-17. doi: 10.1007/s13365-015-0348-9. Epub 2015 May 22.