title: Critical role of microRNA-155 in herpes simplex encephalitis.
abstract: HSV infection of adult humans occasionally results in life-threatening herpes simplex encephalitis (HSE) for reasons that remain to be defined. An animal system that could prove useful to model HSE could be microRNA-155 knockout (miR-155KO) mice. Thus, we observe that mice with a deficiency of miR-155 are highly susceptible to HSE with a majority of animals (75-80%) experiencing development of HSE after ocular infection with HSV-1. The lesions appeared to primarily represent the destructive consequences of viral replication, and animals could be protected from HSE by acyclovir treatment provided 4 d after ocular infection. The miR-155KO animals were also more susceptible to development of zosteriform lesions, a reflection of viral replication and dissemination within the nervous system. One explanation for the heightened susceptibility to HSE and zosteriform lesions could be because miR-155KO animals develop diminished CD8 T cell responses when the numbers, functionality, and homing capacity of effector CD8 T cell responses were compared. Indeed, adoptive transfer of HSV-immune CD8 T cells to infected miR-155KO mice at 24 h postinfection provided protection from HSE. Deficiencies in CD8 T cell numbers and function also explained the observation that miR-155KO animals were less able than control animals to maintain HSV latency. To our knowledge, our observations may be the first to link miR-155 expression with increased susceptibility of the nervous system to virus infection.
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-0845.
authors: Siddheshvar
authors: S
authors: Bhela
authors: Sachin
authors: S
authors: Mulik
authors: Pradeep B J
authors: PB
authors: Reddy
authors: Raphael L
authors: RL
authors: Richardson
authors: Fernanda
authors: F
authors: Gimenez
authors: Naveen K
authors: NK
authors: Rajasagi
authors: Tamara
authors: T
authors: Veiga-Parga
authors: Alexander P
authors: AP
authors: Osmand
authors: Barry T
authors: BT
authors: Rouse
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D020803:Encephalitis, Herpes Simplex / Q000235:genetics* / Q000628:therapy / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D016019:Survival Analysis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D000212:Acyclovir