title: Herpes simplex virus type 1 induces simultaneous activation of Toll-like receptors 2 and 4 and expression of the endogenous ligand serum amyloid A in astrocytes.
abstract: Herpes simplex virus type 1 (HSV-1) is the most common pathogenic cause of sporadic acute encephalitis and it produces latent persistent infection lifelong in infected individuals. Brain inflammation is associated with activation of glial cells, which can detect pathogen-associated molecular patterns (PAMPs) through a variety of pattern-recognition receptors (PRR), including Toll-like receptors (TLRs). In this study, we evaluated the expression and activation of TLR2, TLR3, and TLR4 in HSV-1-infected astrocyte and neuronal primary cultures. Our results showed a clear induction in TLR2 and TLR4 expression in astrocytes as early as 1 h after HSV-1 infection, whereas no significant change was observed in neurons. In addition, infected astrocytes showed increased levels of interferon regulatory factors IRF3 and IRF7, interferon β (INFβ), interleukin 6 (IL6), and serum amyloid A (SAA3) transcripts, as well as phospho-IRF3 protein. These effects seemed to be dependent on viral replication since previous treatment of the cells with acyclovir resulted in low levels of TLRs expression and activation even after 4 h post-infection. These results suggest that reactivation of HSV-1 at the central nervous system (CNS) would likely induce and activate TLR2 and TLR4 receptors directly through interaction of astrocytes with the pathogen and also indirectly by endogenous ligands produced locally, such as serum amyloid protein, potentiating the neuroinflammatory response.
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, P. O. Box 567, Valdivia, Chile.
authors.forename: Melina
authors.initials: M
authors.lastname: Villalba
authors.forename: Melissa
authors.initials: M
authors.lastname: Hott
authors.forename: Carolina
authors.initials: C
authors.lastname: Martin
authors.forename: Blanca
authors.initials: B
authors.lastname: Aguila
authors.forename: Sharin
authors.initials: S
authors.lastname: Valdivia
authors.forename: Claudia
authors.initials: C
authors.lastname: Quezada
authors.forename: Angara
authors.initials: A
authors.lastname: Zambrano
authors.forename: Margarita I
authors.initials: MI
authors.lastname: Concha
authors.forename: Carola
authors.initials: C
authors.lastname: Otth
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology*; D002478:Cells, Cultured; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000821:virology; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D008024:Ligands; D000685:Serum Amyloid A Protein; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4