Medical Microbiology and Immunology

, Volume 201, Issue 3, pp 371–379 | Cite as

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

  • Melina Villalba
  • Melissa Hott
  • Carolina Martin
  • Blanca Aguila
  • Sharin Valdivia
  • Claudia Quezada
  • Ángara Zambrano
  • Margarita I. Concha
  • Carola Otth
Original Investigation


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.


HSV-1 TLRs A-SAA SAA3 Interferon 



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.

Supplementary material

430_2012_247_MOESM1_ESM.doc (1017 kb)
Supplementary material 1 (DOC 1,017 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Melina Villalba
    • 1
  • Melissa Hott
    • 1
  • Carolina Martin
    • 1
  • Blanca Aguila
    • 1
  • Sharin Valdivia
    • 1
  • Claudia Quezada
    • 2
    • 3
  • Ángara Zambrano
    • 2
  • Margarita I. Concha
    • 2
  • Carola Otth
    • 1
    • 3
  1. 1.Instituto de Microbiología Clínica, Facultad de MedicinaUniversidad Austral de ChileValdiviaChile
  2. 2.Instituto de Bioquímica y Microbiología, Facultad de CienciasUniversidad Austral de ChileValdiviaChile
  3. 3.Centro de Investigación Sur-Austral en Enfermedades del Sistema Nervioso (CISNE)Universidad Austral de ChileValdiviaChile

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