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

Investigators:

Georg Kochs

Valentina Wagner

Katharina Geiger

In collaboration with:

• Dr. Zoe Waibler, Paul-Ehrlich-Institut, Langen: Interferon-inducing capacity of Thogoto virus
• Dr. Boris Klempa, Slovak Academy of Sciences, Bratislava, Slovakia: THOV replication in ticks
• Prof. P. Staeheli, Department of Virology, Freiburg: Virulenz and pathogenesis of THOV

Abstract:

Thogoto virus (THOV) is a member of the orthomyxovirus family in addition to the Influenzaviruses. It has a genome of six single-stranded RNA segments with negative polarity. THOV is transmitted by ticks and replicates in both vertebrate and tick cells. It is sensitive to the antiviral action of interferon (IFN), namely the antiviral function of the Mx proteins. Therefore, the virus evolved an IFN antagonist, the viral ML protein, to prevent IFN induction. Using reverse genetics systems for THOV, we are currently investigating the mechanism of ML action. ML blocks the transcriptional activation of type I IFN genes by preventing the activation of the IFN stimulatory factor-3 and 7 (IRF3/7). For this activity, the interaction of ML with the general transcription factor TFIIB seems to be necessary. Comparison of ML action with that of the IFN-antagonistic activity of NS1 of influenza A viruses reveals that orthomyxoviruses evolved different strategies to circumvent the induction of the antiviral host response. In future studies, we will work on factors, like TFIIB, that are directly affected by the ML function.

Selected References

• Kochs, G., Bauer, S., Vogt, C., Frenz, T., Tschopp, J., Kalinke, U., and Waibler, Z
  Thogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells
  J. Virol. 84, 12344-12350 (2010)
  >PubMed
  
  
• Buettner, N., Vogt, C., Martínez-Sobrido, L., Weber, F., Waibler, Z., Kochs, G.
  Thogoto virus ML protein is a potent inhibitor of the IRF7 transcription factor
  J. Gen. Virol., 91, 220-227 (2010)
  >PubMed
  
  
• Vogt, C., Preuss, E., Mayer, D., Weber, F., Schwemmle, M., Kochs, G.
  The Interferon Antagonist ML Protein of Thogoto Virus Targets General Transcription Factor IIB
  J Virol 82: 11446-11453 (2008)
  >PubMed
  
  
• Haller, O., Kochs, G., Weber, F. (Review)
  The interferon response circuit: Induction and suppression by pathogenic viruses
  Virology 344: 119-130 (2006)
  >PubMed
  
  
• Jennings, St., Martínez-Sobrido, L., García-Sastre, A., Weber, F., Kochs, G.
  Thogoto virus ML protein suppresses IRF3 function
  Virology, 331: 63-72 (2005)
  >PubMed
  
  
• Pichlmair, A., Buse, J., Jennings, St., Haller, O., Kochs, G., Staeheli, P.
  Thogoto Virus lacking interferon-antagonistic protein ML is strongly attenuated in newborn Mx1-negative mice
  J Virol 78: 11422-11424 (2004)
  >PubMed
  
  
• Haller, O., Kochs, G.
  Thogotovirus
  In: Tidona, C.A., Darai, G. (Hrsg.). The Springer Index of Viruses. Springer-Verlag, Berlin, Heidelberg, New York, 615-619 (2002) (not available)
  
  

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