Tick-borne flaviviruses: dissecting host immune responses and virus countermeasures

• Published in: Immunologic research Vol. 43; no. 1-3; pp. 172 - 186
• Main Authors: Robertson, Shelly J., Mitzel, Dana N., Taylor, R. Travis, Best, Sonja M., Bloom, Marshall E.
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 2009; Springer Nature B.V
• Subjects: Allergology; Animals; Biomedical and Life Sciences; Biomedicine; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - virology; Disease Vectors; Encephalitis Viruses, Tick-Borne - immunology; Encephalitis Viruses, Tick-Borne - pathogenicity; Encephalitis, Tick-Borne - immunology; Encephalitis, Tick-Borne - transmission; Encephalitis, Tick-Borne - virology; Flavivirus; Humans; Immunity, Innate; Immunology; Interferon; Interferons - immunology; Interferons - metabolism; Internal Medicine; Ixodidae; Janus Kinases - immunology; Janus Kinases - metabolism; Medicine/Public Health; Neurological disorders; Parasites; Pathogens; Receptors, Pattern Recognition - immunology; Receptors, Pattern Recognition - metabolism; Signal Transduction - immunology; STAT Transcription Factors - immunology; STAT Transcription Factors - metabolism; Tick-borne encephalitis virus; Ticks - virology; Viral Envelope Proteins - immunology; Viral Envelope Proteins - metabolism; Viral Nonstructural Proteins - immunology; Viral Nonstructural Proteins - metabolism; Viral Vaccines - immunology; Viruses; tick vector; Interferon antagonism; Tick-borne flavivirus; Dendritic cells
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-008-8065-6

The tick-borne encephalitis (TBE) serocomplex of viruses, genus Flavivirus , includes a number of important human pathogens that cause serious neurological illnesses and hemorrhagic fevers. These viruses pose a significant public health problem due to high rates of morbidity and mortality, their emergence to new geographic areas, and the recent rise in the incidence of human infections. The most notable member of the TBE serocomplex is tick-borne encephalitis virus (TBEV), a neurotropic flavivirus that causes debilitating and sometimes fatal encephalitis. Although effective prophylactic anti-TBEV vaccines have been developed, there is currently no specific treatment for infection. To identify new targets for therapeutical intervention, it is imperative to understand interactions between TBEV and the host immune response to infection. Interferon (IFN) has a critical role in controlling flavivirus replication. Dendritic cells (DCs) represent an early target of TBEV infection and are major producers of IFN. Thus, interactions between DCs, IFN responses, and the virus are likely to substantially influence the outcome of infection. Early IFN and DC responses are modulated not only by the virus, but also by the tick vector and immunomodulatory compounds of tick saliva inoculated with virus into the skin. Our laboratory is examining interactions between the triad of virus, tick vector, and mammalian host that contribute to the pathogenesis of tick-borne flaviviruses. This work will provide a more detailed understanding of early events in virus infection and their impact on flavivirus pathogenesis.