ID: 136: Differential innate immune responses in various brain regions regulate antiviral response in the CNS during Tick-borne encephalitis virus infection

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• 作者：Loreen Zegenhagen¹ ; ; Elvira Weber³ ; Chaitanya Kurade² ; Sharmila Nair⁴ ; Anna K. Ö ; verby² ; Andrea Krö ; ger⁵ ; Andrea Krö ; ger¹
• 刊名：Cytokine
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：76
• 期：1
• 页码：91
• 全文大小：45 K

文摘

Tick-borne encephalitis virus (TBEV), a member of the flavivirus family, causes infections with a variety of symptoms like hemorrhagic fevers, encephalitis and meningitis in the human host. Despite an available vaccine, thousands of new TBEV cases occur each year and therapy is restricted to symptomatic treatment. However, little is known about the innate response of the host to TBEV infection, especially subsequent to invasion of the central nervous system (CNS). Langat virus (LGTV), a naturally attenuated virus of this group, is recognized by Retinoic-acid inducible gene I like receptors (e.g. MDA-5/RIG-I). Subsequently, adaptor molecule IFN-β$\mathrm{\beta }$ promotor stimulator-1 (IPS-1) is activated and induces production of Type I Interferons. Secreted Interferon binds the IFN-α$\mathrm{\alpha }$ receptor (IFNAR, leading to signal amplification and activation of a high variety of antiviral genes.

We found that mice defective in IPS-1 and IFNAR are highly susceptible to LGTV infections. Local production of Type I IFN in the CNS is crucial for restriction of the virus. Uncontrolled virus replication leads to breakdown of the blood–brain barrier, infiltration of inflammatory leukocytes into the brain and upregulation of ISGs like Mx, Viperin and CXCL10.

Interestingly, Interferon is regulated differently in distinct brain parts. The antiviral innate immunity in the olfactory bulb is cleary dependent on IPS-1, whereas its role in other brain parts is less important. In summary our data show that innate antiviral immunity is essential in local control of TBEV and LGTV in the CNS and that the antiviral response is differentially regulated in various brain regions.