Type I interferon protects mice from fatal neurotropic infection with langat virus by systemic and local antiviral responses

Elvira Weber, Katja Finsterbusch, Richard Lindquist, Sharmila Nair, Stefan Lienenklaus, Nelson O. Gekara, Dirk Janik, Siegfried Weiss, Ulrich Kalinke, Anna K. Överby, Andrea Kröger

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Vector-borne flaviviruses, such as tick-borne encephalitis virus (TBEV), West Nile virus, and dengue virus, cause millions of infections in humans. TBEV causes a broad range of pathological symptoms, ranging from meningitis to severe encephalitis or even hemorrhagic fever, with high mortality. Despite the availability of an effective vaccine, the incidence of TBEV infections is increasing. Not much is known about the role of the innate immune system in the control of TBEV infections. Here, we show that the type I interferon (IFN) system is essential for protection against TBEV and Langat virus (LGTV) in mice. In the absence of a functional IFN system, mice rapidly develop neurological symptoms and succumb to LGTV and TBEV infections. Type I IFN system deficiency results in severe neuroinflammation in LGTV-infected mice, characterized by breakdown of the blood-brain barrier and infiltration of macrophages into the central nervous system (CNS). Using mice with tissue-specific IFN receptor deletions, we show that coordinated activation of the type I IFN system in peripheral tissues as well as in the CNS is indispensable for viral control and protection against virus induced inflammation and fatal encephalitis.

Original languageEnglish
Pages (from-to)12202-12212
Number of pages11
JournalJournal of virology
Volume88
Issue number21
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint Dive into the research topics of 'Type I interferon protects mice from fatal neurotropic infection with langat virus by systemic and local antiviral responses'. Together they form a unique fingerprint.

  • Cite this

    Weber, E., Finsterbusch, K., Lindquist, R., Nair, S., Lienenklaus, S., Gekara, N. O., Janik, D., Weiss, S., Kalinke, U., Överby, A. K., & Kröger, A. (2014). Type I interferon protects mice from fatal neurotropic infection with langat virus by systemic and local antiviral responses. Journal of virology, 88(21), 12202-12212. https://doi.org/10.1128/JVI.01215-14