A5041242389- Viral Infections and Outbreaks Research
- Bacillus and Francisella bacterial research
- Viral Infections and Vectors
- Hepatitis B Virus Studies
- Fire effects on ecosystems
- Viral gastroenteritis research and epidemiology
- Mosquito-borne diseases and control
- Plant Virus Research Studies
- Virus-based gene therapy research
- Bacteriophages and microbial interactions
- Photosynthetic Processes and Mechanisms
- Aquatic and Environmental Studies
- Protein purification and stability
- Hemoglobinopathies and Related Disorders
- Water Resources and Management
- Plant and fungal interactions
- Legume Nitrogen Fixing Symbiosis
- Influenza Virus Research Studies
- Hemoglobin structure and function
- Horticultural and Viticultural Research
- Botany and Plant Ecology Studies
- Soil and Environmental Studies
- Neonatal Health and Biochemistry
Bernhard Nocht Institute for Tropical Medicine
2017-2024
Technische Universität Berlin
2013
University of Regensburg
1975-1981
University of Stuttgart
1981
University of Milan
1981
European Molecular Biology Organization
1981
Abstract The Bunyavirales order contains several emerging viruses with high epidemic potential, including Severe fever thrombocytopenia syndrome virus (SFTSV). lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment any outbreak. To develop antivirals profound understanding viral replication process essential. L protein bunyaviruses multi-functional multi-domain performing both transcription genome and, therefore, an ideal drug target. We...
Abstract Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures L states process, from pre-initiation to late-stage elongation, at resolution up 2.6 Å. We identify how binds 5′ hook-like...
Lassa virus is endemic in West Africa and can cause severe hemorrhagic fever. The viral L protein transcribes replicates the RNA genome via its RNA-dependent polymerase activity. Here, we present nine cryo-EM structures of apo-, promoter-bound pre-initiation active synthesis states. We characterize distinct binding pockets for conserved 3' 5' promoter RNAs show how full-promoter induces a conformation. In apo- early elongation states, endonuclease inhibited by two peptides, whereas state it...
Crocodilian hemoglobin has a high intrinsic oxygen affinity but does not react with those organic phosphate esters that normally control the of blood in higher vertebrates.Instead, its is greatly lowered by CO,.The present study was undertaken to determine nature COZ binding crocodilian species, Caiman, both qualitatively and quantitatively.The following parameters were measured: (a) carbamino compounds deoxy-and oxyhemoglobin, (b) effect (at constant pH) on Caiman hemoglobin, (c) total CO,...
The L protein of arena- and bunyaviruses is structurally functionally related to the orthomyxovirus polymerase complex. It plays a central role in viral life cycle, as it replicates virus genome generates mRNA via cap-snatching mechanism. Here, we aimed biochemically characterize Lassa virus, human-pathogenic arenavirus endemic West Africa. Full-length 250-kDa was expressed using baculovirus expression system. A low-resolution structure calculated from small-angle X-ray scattering data...
Cap-snatching was first discovered in influenza virus. Structures of the involved domains virus polymerase, namely endonuclease PA subunit and cap-binding domain PB2 subunit, have been solved. endonucleases also demonstrated at very N-terminus L proteins mammarena-, orthobunya-, hantaviruses. However, a has not identified an arena- or bunyavirus protein so far. We solved structure 326 C-terminal residues California Academy Sciences (CASV), reptarenavirus, by X-ray crystallography. The...
The Bunyavirales order is a large and diverse group of segmented negative-strand RNA viruses. Several virus families within this contain important human pathogens, including Sin Nombre (SNV) the Hantaviridae . Despite high epidemic potential bunyaviruses, specific medical countermeasures such as vaccines or antivirals are missing. multifunctional ~250 kDa L protein hantaviruses, amongst other functional domains, harbors RNA-dependent polymerase (RdRp) an endonuclease catalyzes transcription...
Abstract Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that now endemic to several East Asian countries. The viral large (L) protein catalyzes transcription by stealing host mRNA caps via process known as cap-snatching. Here, we establish an in vitro cap-snatching assay and present three high-quality electron cryo-microscopy (cryo-EM) structures of the SFTSV L biologically relevant, transcription-specific states. In priming-state structure, show capped RNA...
Lassa virus is a negative-strand RNA with only four structural proteins that causes periodic outbreaks in West Africa. The nucleoprotein (NP) encapsidates the viral genome, forming ribonucleoprotein complexes (RNPs) together and L protein. RNPs must be continuously restructured during genome replication transcription. Z protein important for membrane recruitment of RNPs, particle assembly, budding has also been shown to interact However, interaction NP, RNA, poorly understood. Here, we...
Abstract Lassa virus is a negative-strand RNA with only four structural proteins that causes periodic outbreaks in West Africa. The nucleoprotein (NP) encapsidates the viral genome, forming ribonucleoprotein complexes (RNPs) together and L protein. RNPs have to be continuously restructured during genome replication transcription. Z protein important for membrane recruitment of RNPs, particle assembly budding, has also been shown interact However, interaction NP, poorly understood. Here, we...
ABSTRACT Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that now endemic to several East Asian countries. The viral large (L) protein catalyzes transcription by stealing host mRNA caps via process known as cap-snatching. Here, we establish an in vitro cap-snatching assay and present three high-quality electron cryo-microscopy (cryo-EM) structures of the SFTSV L biologically relevant, transcription-specific states. In priming-state structure, show capped RNA...
Bunyaviruses constitute a large and diverse group of viruses encompassing many emerging pathogens, such as Rift Valley fever virus (family Phenuiviridae), with public veterinary health relevance but very limited medical countermeasures are available. For the development antiviral strategies, identification validation virus-specific targets would be high value. The cap-snatching mechanism is an essential process in life cycle bunyaviruses to produce capped mRNAs, which then recognized...
Abstract Lassa virus, which causes annual outbreaks in West Africa with increasing case numbers recent years, is recognized by the WHO R&D blueprint as a significant threat for public health high epidemic potential and no effective countermeasures. The viral large (L) protein, contains RNA-dependent RNA polymerase, key player transcription of mRNA genome replication. Here we present nine cryo-EM structures virus L protein apo-, promoter-bound pre-initiation active synthesis states. We...
ABSTRACT The Bunyavirales order contains several emerging viruses with high epidemic potential, including Severe fever thrombocytopenia syndrome virus (SFTSV). lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment any outbreak. To develop antivirals profound understanding viral replication process essential. L protein bunyaviruses multi-functional multi-domain performing both transcription genome and, therefore, would be an ideal drug...
ABSTRACT Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures L states process, from pre-initiation to late-stage elongation, at resolution up 2.6 Å. We identify how binds 5′ hook-like...