A5066958566- Influenza Virus Research Studies
- Animal Disease Management and Epidemiology
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- RNA regulation and disease
- Diabetes and associated disorders
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- Neuroscience of respiration and sleep
University of Freiburg
2018-2024
University Medical Center Freiburg
2018-2024
Zoonotic avian influenza A virus (IAV) infections are rare. Sustained transmission of these IAVs between humans has not been observed, suggesting a role for host genes. We used whole-genome sequencing to compare IAV H7N9 patients with healthy controls and observed strong association infection rare, heterozygous single-nucleotide variants in the MX1 gene. codes myxovirus resistance protein (MxA), an interferon-induced antiviral guanosine triphosphatase known control transgenic mice. Most MxA...
MxA inflammasome restricts influenza A virus infection in respiratory epithelium.
Abstract Mitochondria react to infection with sub-lethal signals in the apoptosis pathway. Mitochondrial can be inflammatory but mechanisms are only partially understood. We show that activation of caspase-activated DNase (CAD) mediates mitochondrial pro-inflammatory functions and substantially contributes host defense against viral infection. In cells lacking CAD, activity was reduced. Experimental CAD caused transient DNA-damage a pronounced DNA damage response, involving major kinase...
The human MxA protein efficiently blocks the replication of IAV from nonhuman species. In rare cases, however, these overcome species barrier and become pandemic. All known pandemic viruses have acquired maintained escape mutations in viral NP thus are not controlled by MxA. Intriguingly, partial resistance can also be other hosts that express antivirally active Mx proteins, such as swine. To perform a risk assessment circulating European swine population, we analyzed degree Eurasian...
Interferon (IFN) induction of IFN-stimulated genes (ISGs) creates a formidable protective antiviral state. However, loss appropriate control mechanisms can result in constitutive pathogenic ISG upregulation. Here, we used genome-scale loss-of-function screening to establish critical for IFN-induced transcription, identifying all expected members the JAK-STAT signaling pathway and previously unappreciated epigenetic reader, bromodomain-containing protein 9 (BRD9), defining subunit...
The interferon-induced myxovirus resistance protein A (MxA) is a potent restriction factor that prevents zoonotic infection from influenza virus (IAV) subtype H7N9. Individuals expressing antivirally inactive MxA variants are highly susceptible to these infections. However, human-adapted IAVs have acquired specific mutations in the viral nucleoprotein (NP) allow escape MxA-mediated but not been observed MxA-sensitive, human H7N9 isolates. To date, it unknown whether can adapt restriction....
Abstract Exchange of viral segments between one or more influenza virus subtypes can contribute to a shift in virulence and adaptation new hosts. Among several subtypes, H9N2 is widely circulating poultry populations worldwide has the ability infect humans. Here, we studied reassortant compatibility chicken with N1–N9 gene wild bird origin, either an intact truncated stalk. Naturally occurring amino acid deletions NA stalk lead increased both mallard ducks chickens. Our findings show...
Abstract Swine influenza A virus (swIAV) infections in pig populations cause considerable morbidity and economic losses. Frequent reverse zoonotic incursions of human IAV boost reassortment opportunities with authentic porcine avian-like swine herds potentially enhancing even pre-pandemic potential. Vaccination using adjuvanted inactivated full vaccines is frequently used attempting control swIAV infections. Accelerated antigenic drift large holdings interference maternal antibodies vaccine...
ABSTRACT Transient interferon (IFN) induction of IFN-stimulated genes (ISGs) creates a formidable protective antiviral state. However, loss appropriate control mechanisms can result in constitutive pathogenic ISG upregulation. Here, we used genome-wide loss-of-function screening to establish critical for IFN signaling, identifying all expected members the JAK-STAT pathway and previously unappreciated bromodomain-containing protein 9 (BRD9), defining subunit non-canonical BAF (ncBAF)...