Arbeitsgruppe Prof. Dr. Friedemann Weber
Dr. Friedemann Weber
Institute for Virology
FB10 – Veterinary Medicine
Justus-Liebig University Gießen
Tel.: +49-641-99 383 50
Tel.: +49-641-99 383 51 (Sekretariat)
Institute for Virology
Phone: ++49 6421 / 28-64525
Fax: ++49 6421 / 28-68962
- Dr. Stephanie Devignot
- Dr. Andreas Schön
- Simone Lau
- Jennifer Deborah Würth
Diploma, Bachelor- and Masterstudents
- Julia Wulle
Liste der Publikationen auf PubMed
Project 1. Reverse genetics and molecular biology of bunyaviruses
The family Bunyaviridae contains several serious human pathogens, causing encephalitis, febrile illnesses or hemorrhagic fevers. Important members are La Crosse virus, Oropouche virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus and the Hantaviruses. All bunyaviruses are enveloped and have a tri-segmented single-stranded RNA genome of negative or ambisense polarity, replicate in the cytoplasm, and bud into the Golgi apparatus. For the targeted mutagenesis of viruses, the rescue of infectious viruses entirely from cloned cDNA plasmids ("reverse genetics") is mandatory. The so-called minireplicon systems represent the first step towards bunyavirus reverse genetics. Minireplicon systems are used to reconstitute recombinant viral nucleocapsids containing an artificial, genome-like reporter RNA (minireplicon). If the minireplicon is replaced by full-length cDNA constructs of the viral gene segments, infectious viruses can be recovered. Using these methods, we study the replication, host cell interactions, and virulence mechanisms of bunyaviruses.
Project 2. SARS-coronavirus and the antiviral type I interferon system
Type I interferons (IFN-alpha and beta) are the only licenced drugs against SARS-coronavirus (SARS-CoV). IFNs are normally produced by virus-infected cells, causing neighbour cells to express a range of IFN-stimulated genes (ISGs) with antiviral activity. However, we have shown that SARS-CoV-infected cells are unable to secrete IFN because the virus blocks the IFN promoter by targeting the transcription factor IRF-3. Our ongoing projects are aimed at identifying (i) the viral factors and mechanisms which block IRF-3, and (ii) the antiviral ISG responsible for inhibiting SARS-CoV. These experiments may reveal important SARS-CoV virulence mechanisms as well as anti-SARS restriction factors and allow implications for viral transmission and host selection. The IFN-sensitive SARS-CoV mutants generated during this project could be promising candidates for live vaccines.
Project 3. Induction of and inhibition of intracellular pathways triggering interferon induction
Host defences to RNA viruses are highly dependent on a rapid detection of the pathogen. In tissue cells, recognition of infection occurs mainly by an intracellular pathway. Two cytoplasmic RNA helicases, RIG-I and MDA5 (collectively termed RIG-like receptors, RLRs), are the main intracellular receptors of viral RNA. RIG-I responds mainly to RNA molecules with a triphosphorylated 5’ (5’-PPP) end, whereas MDA5 activation is more dependent on long and branched double-stranded (ds) RNA structures. The binding of a viral RNA to these pathogen recognition receptors (PRRs) induces a signalling chain which eventually results in the activation of the genes for type I interferons (IFN-alpha and beta). IFNs in turn are secreted and trigger a cascade of antiviral factors and activities in their target cells. The aim of this project is to elucidate the various mechanisms leading to RLR activation, and to investigate viral measures inhibiting this important signalling pathway. For these studies we are mainly, but not exclusively, using the molecular tools and viral systems which were developed for projects 1 and 2.