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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

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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.

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Acknowledgments

The study was supported by Fondecyt Project 11080067 and DID-UACH S-2009-40.

Conflict of interest

The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, P. O. Box 567, Valdivia, Chile

    Melina Villalba, Melissa Hott, Carolina Martin, Blanca Aguila, Sharin Valdivia & Carola Otth

  2. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile

    Claudia Quezada, Ángara Zambrano & Margarita I. Concha

  3. Centro de Investigación Sur-Austral en Enfermedades del Sistema Nervioso (CISNE), Universidad Austral de Chile, Valdivia, Chile

    Claudia Quezada & Carola Otth

Authors
  1. Melina Villalba
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  2. Melissa Hott
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  3. Carolina Martin
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  9. Carola Otth
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Correspondence to Carola Otth.

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Villalba, M., Hott, M., Martin, C. et al. 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. Med Microbiol Immunol 201, 371–379 (2012). https://doi.org/10.1007/s00430-012-0247-0

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  • DOI: https://doi.org/10.1007/s00430-012-0247-0

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