title: Inflammatory and neurodegeneration markers during asymptomatic HSV-1 reactivation.
abstract: BACKGROUND
  Currently, it is unclear whether asymptomatic recurrent reactivations of herpes simplex virus type 1 (HSV-1) occur in the central nervous systems of infected people, and if these events could lead to a progressive deterioration of neuronal function. In this context, HSV-1 constitutes an important candidate to be included among the risk factors for the development of neuropathies associated with chronic neuroinflammation.
  
  
  OBJECTIVE
  The aim of this study was to assess in vivo inflammatory and neurodegenerative markers in the brain during productive and latent HSV-1 infection using a mouse model of herpes simplex encephalitis.
  
  
  METHODS
  Neuroinflammation and neurodegeneration markers were evaluated in mice trigeminal ganglia and cerebral cortex during HSV-1 infection, by immunohistochemistry, western blot, and RT-PCR.
  
  
  RESULTS
  Neuronal ICP4 viral antigen expression indicative of a reactivation episode during asymptomatic latency of HSV-1 infection in mice was accompanied by upregulation of neuroinflammatory (toll-like receptor-4, interferon α/β, and p-IRF3) and early neurodegenerative markers (phospho-tau and TauC3).
  
  
  CONCLUSIONS
  HSV-1 reactivation from latency induced neuroinflammatory and neurodegenerative markers in the brain of asymptomatic mice suggesting that recurrent reactivations could be associated with cumulative neuronal dysfunctions.
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martin
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Blanca
authors.initials: B
authors.lastname: Aguila
authors.affiliation: Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Araya
authors.affiliation: Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Karin
authors.initials: K
authors.lastname: Vio
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Sharin
authors.initials: S
authors.lastname: Valdivia
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Angara
authors.initials: A
authors.lastname: Zambrano
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Margarita I
authors.initials: MI
authors.lastname: Concha
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile Centro de Investigación Sur-Austral en Enfermedades del Sistema Nervioso (CISNE), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carola
authors.initials: C
authors.lastname: Otth
mesh_terms: D000818:Animals; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006561:Herpes Simplex / Q000378:metabolism* / Q000473:pathology*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity* / Q000502:physiology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014775:Virus Activation / Q000502:physiology*
chemical_list: D015415:Biomarkers
keywords: Herpes simplex encephalitis; TauC3; herpes simplex virus type 1; neurodegeneration; neuroinflammation; toll-like receptor 4; trigeminal ganglion