Research area: Molecular Virology
A key virulence factor of bunyaviruses is the non-structural protein NSs, an inhibitor of the antiviral type I interferon (IFN-alpha/beta) system. Previously, the Weber group demonstrated that NSs of Rift valley fever virus (RVFV) blocks the induction of IFN on the transcriptional level, and degrades the antiviral IFN effector PKR via the proteasome. It remained however unclear how IFN induction and PKR activation occur at all, and how NSs counteracts these processes. In the first CRC 1021 funding period, the Weber group identified two regulatory dsRNA structures, namely the “panhandle” and the intergenic region (IGR) of the viral genome, as activators of RIG-I (and hence IFN induction) and PKR, respectively. Moreover, they discovered that RVFV NSs recruits the cellular F-box type ubiquitin ligase subunits FBXO3 and FBXW11/beta-TRCP1 to destroy the general host cell transcription factor TFIIB-p62 (involved in IFN gene induction) and PKR, respectively. In addition, the Weber group observed that RVFV NSs impairs the nuclear export of host mRNAs and that NSs from other bunyaviruses use different mechanisms to block IFN response and PKR activation in infected cells. Project-related publications of the investigator:
- Ferron F, Weber F, de la Torre JC, Reguera J. 2017. Transcription and replication mechanisms of Bunyaviridae and Arenaviridae L proteins. Virus Res 234:118-134.
- Frantz R, Teubner L, Schultze T, La Pietra L, Muller C, Gwozdzinski K, Pillich H, Hain T, Weber-Gerlach M, Panagiotidis GD, Mostafa A, Weber F, Rohde M, Pleschka S, Chakraborty T, Abu Mraheil M. 2019. The secRNome of Listeria monocytogenes Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon. mBio 10:e01223-19
- Holzer M, Schoen A, Wulle J, Muller MA, Drosten C, Marz M, Weber F. 2019. Virus- and Interferon Alpha-Induced Transcriptomes of Cells from the Microbat Myotis daubentonii. iScience 19:647-661.
- Jones R, Lessoued S, Meier K, Devignot S, Barata-Garcia S, Mate M, Bragagnolo G, Weber F, Rosenthal M, Reguera J. 2019. Structure and function of the Toscana virus cap-snatching endonuclease. Nucleic Acids Research 47:10914-10930.
- Kiening M, Weber F, Frishman D. 2017. Conserved RNA structures in the intergenic regions of ambisense viruses. Sci Rep 7:16625.
- Lau S, Weber F. 2020. Nuclear pore protein Nup98 is involved in replication of Rift Valley fever virus and nuclear import of virulence factor NSs. J Gen Virol 101:712-716.
- Mostajo NF, Lataretu M, Krautwurst S, Mock F, Desiro D, Lamkiewicz K, Collatz M, Schoen A, Weber F, Marz M, Holzer M. 2020. A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes. NAR Genom Bioinform 2:lqz006.
- Schoen A, Lau S, Verbruggen P, Weber F. 2020. Elongin C Contributes to RNA Polymerase II Degradation by the Interferon Antagonist NSs of La Crosse Orthobunyavirus. J Virol 94.
- Wuerth JD, Habjan M, Wulle J, Superti-Furga G, Pichlmair A, Weber F. 2018. NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN) Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3. J Virol 92.
- Wuerth JD, Habjan M, Kainulainen M, Berisha B, Bertheloot D, Superti-Furga G, Pichlmair A, Weber F. 2020. eIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition. mBio 11:e00976-20