TY - JOUR
T1 - Type I interferon protects mice from fatal neurotropic infection with langat virus by systemic and local antiviral responses
AU - Weber, Elvira
AU - Finsterbusch, Katja
AU - Lindquist, Richard
AU - Nair, Sharmila
AU - Lienenklaus, Stefan
AU - Gekara, Nelson O.
AU - Janik, Dirk
AU - Weiss, Siegfried
AU - Kalinke, Ulrich
AU - Överby, Anna K.
AU - Kröger, Andrea
N1 - Publisher Copyright:
© 2014, American Society for Microbiology.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907963247&partnerID=8YFLogxK
U2 - 10.1128/JVI.01215-14
DO - 10.1128/JVI.01215-14
M3 - Article
C2 - 25122777
AN - SCOPUS:84907963247
VL - 88
SP - 12202
EP - 12212
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 21
ER -