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Thogoto Virus: Molecular Biology of a Tick-Transmitted Orthomyxovirus.


Thogotoviruses belong to the Orthomyxoviridae family in addition to the better known Influenza viruses that cause seasonal epidemics in humans.

In contrast to FLU-viruses, Thogotoviruses are arboviruses, meaning they rely on arthropod vectors for transmission between mammalian hosts. For most Thogotoviruses different ticks were identified as vector species.

Sporadic infections of humans and wild or domestic animals have been reported since the discovery of Thogotoviruses in the 1960’s in the Thogoto forest near Nairobi, Kenya. In recent years however, the zoonotic potential of these viruses has become more apparent after the previously unknown Bourbon virus was associated with the death of two patients in the US-Midwest.

With the increasing exposure of humans and domestic animals to ticks and the advance of invasive tick species due to habitat destruction and changing climate, zoonotic transmission events by Thogotoviruses might become more frequent in the future.

The aim of our project is to improve the understanding of the molecular biology and pathology of this unconventional class of orthomyxoviruses.

Like other Orthomyxoviruses, Thogotoviruses have a segmented genome of single stranded negative sense-RNA. Together, the six genome segments encode for 6-7 viral proteins:

The three largest segments contain the information for the subunits, PB1, PB2, and PA, that make up the viral RNA-dependent RNA polymerase (RdRP) responsible for replication of the viral genome and its transcription into positive-sense mRNA.

The fourth and fifth largest segments respectively encode a Glycoprotein (GP), the surface protein responsible for attachment and entry into the host cell, and the nucleoprotein (NP), which encapsidates and protects the viral RNA, forming the viral Ribonucleocapsid (vRNP). The smallest segment codes for the viral Matrix protein (M) responsible for packaging of the genome segments into newly forming viral particles. In some Thogotoviruses, this segment also contains the information for an accessory protein called Matrix long (ML) with immune-modulatory functions.

Our current research focuses on the intricate coding strategy of the smaller genome segments of Thogotoviruses as well as the interplay of Thogotoviruses with parts of the host innate immune system, such as the interferon-induced Mx-proteins.

Selected References

  • Fuchs, J., Lamkiewicz, K., Kolesnikova, L., Hölzer, M., Marz, M., & Kochs, G. (2022). Comparative Study of Ten Thogotovirus Isolates and Their Distinct In Vivo Characteristics. Journal of virology, 96(5), e0155621. https://doi.org/10.1128/JVI.01556-21
  • Fuchs, J., Oschwald, A., Graf, L., & Kochs, G. (2020). Tick-transmitted thogotovirus gains high virulence by a single MxA escape mutation in the viral nucleoprotein. PLoS pathogens, 16(11), e1009038. https://doi.org/10.1371/journal.ppat.1009038
  • Fuchs, J., Straub, T., Seidl, M., & Kochs, G. (2019). Essential Role of Interferon Response in Containing Human Pathogenic Bourbon Virus. Emerging infectious diseases, 25(7), 1304–1313. https://doi.org/10.3201/eid2507.181062
  • Spitaels, J., Van Hoecke, L., Roose, K., Kochs, G., & Saelens, X. (2019). Mx1 in Hematopoietic Cells Protects against Thogoto Virus Infection. Journal of virology, 93(15), e00193-19. https://doi.org/10.1128/JVI.00193-19
  • Haas, D. A., Meiler, A., Geiger, K., Vogt, C., Preuss, E., Kochs, G., & Pichlmair, A. (2018). Viral targeting of TFIIB impairs de novo polymerase II recruitment and affects antiviral immunity. PLoS pathogens, 14(4), e1006980. https://doi.org/10.1371/journal.ppat.1006980
  • Kochs, G., Anzaghe, M., Kronhart, S., Wagner, V., Gogesch, P., Scheu, S., Lienenklaus, S., & Waibler, Z. (2016). In Vivo Conditions Enable IFNAR-Independent Type I Interferon Production by Peritoneal CD11b+ Cells upon Thogoto Virus Infection. Journal of virology, 90(20), 9330–9337. https://doi.org/10.1128/JVI.00744-16
  • Patzina, C., Haller, O., & Kochs, G. (2014). Structural requirements for the antiviral activity of the human MxA protein against Thogoto and influenza A virus. The Journal of biological chemistry, 289(9), 6020–6027. https://doi.org/10.1074/jbc.M113.543892
  • Vogt, C., Preuss, E., Mayer, D., Weber, F., Schwemmle, M., & Kochs, G. (2008). The interferon antagonist ML protein of thogoto virus targets general transcription factor IIB. Journal of virology, 82(22), 11446–11453. https://doi.org/10.1128/JVI.01284-08
  • Hagmaier, K., Jennings, S., Buse, J., Weber, F., & Kochs, G. (2003). Novel gene product of Thogoto virus segment 6 codes for an interferon antagonist. Journal of virology, 77(4), 2747–2752. doi.org/10.1128/jvi.77.4.2747-2752.2003

Institute of Virology

Hermann-Herder-Strasse 11
D-79104 Freiburg


Prof. Dr. med. Hartmut Hengel