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Title [sv]
Försvarsmekanismer som hindrar virusinfektion av hjärnan
Title [en]
Antiviral defense mechanisms in the portal to the brain
Abstract [en]
Many neurotropic viruses enter the brain via olfactory sensory neurons linking the nasal cavity to the olfactory bulb (OB) in the central nervous system (CNS). The rarity of viral CNS infections suggest that the OB provide neuroprotective immunity, restricting viral access to the brain. We have found that the TBEV related Langat virus upon infection of mice localizes to OB and then is quickly cleared in a type I interferon (IFN) dependent way. We here aim to provide new knowledge of mechanisms critical for the restriction in OB, to be explored for development of antivirals. We employ an in vivo based approach to explore regulation of the IFN response and role of viperin in CNS. We have exciting preliminary data showing differential expression of viral defense factors in primary cells of the mouse brain, favoring the hypothesis of OB as a protective portal. Transcriptomic, and proteomic analyses of primary cells from OB and other parts of CNS combined with assays to determine regulatory pathways are employed. An in vitro cell culture approach aims to elucidate molecular mechanism of the antiviral effector viperin for future utilization as antiviral. Viperin interacting host and also viral proteins have been identified and will be studied further to verify participation and map molecular interactions. Hence, promising data and established methodologies put us in a unique position to take an important next step to understand molecular mechanisms of the brain viral defense.
Principal InvestigatorÖverby Wernstedt, Anna
Coordinating organisation
Umeå University
Funder
Period
2018-01-01 - 2020-12-31
National Category
Microbiology in the medical areaMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
DiVA, id: project:1548Project, id: 2017-02438_VR