title: Nutraceutical activators of AMPK/Sirt1 axis inhibit viral production and protect neurons from neurodegenerative events triggered during HSV-1 infection.
abstract: Herpes simplex virus type-1 (HSV-1) is ubiquitous and is able to establish a lifelong persistent latent infection in neurons of infected individuals. It has been estimated that in approximately 70% of the population over 50 years old, the virus enters the brain and infects neurons, and possibly undergoes recurrent reactivation episodes during lifetime, especially in immunodepressed individuals. We previously showed that the sensors AMP-dependent kinase (AMPK) and Sirtuin 1 (Sirt1), involved in survival pathways and neuroprotection, were affected during the course of HSV-1 infection. To evaluate if natural activators of the AMPK/Sirt1 axis, such as Resveratrol and Quercetin could reduce viral propagation and/or counteract the effects of neuronal infection, we analyzed progeny virion production, neuronal viability and neurodegenerative events during HSV-1 infection. We found that the activators of AMPK/Sirt1 axis, increased the viability of infected neurons, significantly reduced the viral titer in the supernatant and the expression of viral genes. More importantly, pretreatment of neurons with Resveratrol or Quercetin significantly reduced the levels of caspase-3 cleaved- and hyperphosphorylated tau associated with HSV-1 infection. These results suggest that activators of the AMPK/Sirt1 axis could be potentially useful in reducing the risk of HSV-1 productive infection in neurons and the cellular damage associated with reactivation episodes.
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Leyton
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hott
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Acuña
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Caroca
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Nuñez
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 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. Electronic address: cotth@uach.cl.
authors.forename: Carola
authors.initials: C
authors.lastname: Otth
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D019587:Dietary Supplements / Q000032:analysis*; D020536:Enzyme Activators / Q000494:pharmacology*; D006561:Herpes Simplex / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000821:virology*; D011794:Quercetin / Q000494:pharmacology; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D020536:Enzyme Activators; D013267:Stilbenes; D011794:Quercetin; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: AMPK; HSV-1; Quercetin; Resveratrol; Sirt1; p53