title: 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.
abstract: 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.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. Lbenmoha@uci.edu.|Department of Molecular Biology & Biochemistry, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. Lbenmoha@uci.edu.|Institute for Immunology, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. Lbenmoha@uci.edu.|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.
authors.forename: Lbachir
authors.initials: L
authors.lastname: BenMohamed
authors.affiliation: 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.
authors.forename: Nelson
authors.initials: N
authors.lastname: Osorio
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA.
authors.forename: Arif A
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Gavin Herbert Eye Institute and Department of Ophthalmology, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Simpson
authors.affiliation: 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.|Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, 92697, USA. Wechsler@uci.edu.|Center for Virus Research, University of California Irvine, Irvine, CA, 92697, USA. Wechsler@uci.edu.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human / Q000502:physiology*; D016849:Keratitis, Herpetic / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D014466:Ultraviolet Rays; D014775:Virus Activation / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C477253:latency associated transcript, herpes simplex virus-1
keywords: Animal model; Eye; HSV-1; Immunology; LAT; Recurrent herpetic disease; UV-B; Virology