Viral infection of the brain
PI: Anna Överby Wernstedt, Associate Professor
Department of Clinical Microbiology, Virology
Tick borne encephalitis virus (TBEV) is an important emerging human pathogen. The virus infection causes a broad spectrum of symptoms ranging from mild infections to more severe symptoms such as meningitis, encephalitis, and hemorrhagic fever associated with high mortality rates. The severity of the symptoms is strain dependent.
Whereas TBEV strains from Central Europe often cause milder disease, strains from Siberia and Far Eastern frequently lead to more severe symptoms. The molecular mechanism underlying this virus strain dependency remains elusive. Therefore, we are interested in identifying potential molecular strain differences and correlating them with pathogenicity.
Specific antiviral drugs are still not available and treatment of patients is limited to supportive care only. Although an effective vaccine is available, the number of clinical TBE cases is increasing both in Sweden and all over Europe.
The Överby lab is focusing on different aspects of tick-borne encephalitis virus from molecular virology and host pathogen interactions to pathogenicity and innate immunity by combining different in vivo and in vitro systems.
Tick borne encephalitis virus (TBEV) is an important emerging human pathogen in Europe and Sweden. The virus infection causes a broad spectrum of symptoms ranging from mild infections to more severe symptoms such as meningitis and encephalitis. Specific antiviral drugs are still not available and treatment of patients is limited to supportive care only. Although an effective vaccine is available, both the number of clinical TBE cases and the distribution of endemic region are increasing both in Sweden and in Europe over the last years.
In order to identify new viral targets for antiviral drugs, detailed information is required about the virus life cycle. We are therefore taking a broad approach combining advanced imaging with proteomics and molecular virology to in detail understand viral replication and assembly.
TBEV is a positive-strand virus belonging to the family of flaviviruses. Both the adaptive immune system and a key player of innate immunity, the antiviral interferon (IFN) system, are important for viral clearance. Following virus infection of the host cell, double stranded RNA, produced as a replication intermediate, is recognized by pattern recognition receptors (PRRs). This recognition subsequently leads to activation of the transcription factor IRF-3 which induces IFN production. Secretion of IFN causes the neighboring cells to produce IFN-stimulated genes (ISGs) with a potent antiviral effect. One of them is viperin, viperin is a multifunctional protein and we are only starting to understand the molecular antiviral mechanism of this potent protein against TBEV and other flaviviruses. This work will continue with the aim to identify in detail the antiviral mechanism of viperin. The central nervous system has long been regarded as immune privilege, however, we have seen that the type I IFN system is important for viral clearance. However, the viral tropism, the cell type specific antiviral responses in the CNS that determines the outcome of infection are poorly characterized. These questions will be addressed in different mouse models and in vitro primary cell culture models.
Swedish summary on the research of Anna Överby's group (www.umu.se)
Photo credit: Mattias Petterson.