A5082604979- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- Viral Infections and Vectors
- Animal Virus Infections Studies
- Bacillus and Francisella bacterial research
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Virology and Viral Diseases
- RNA Interference and Gene Delivery
- IL-33, ST2, and ILC Pathways
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Immune Cell Function and Interaction
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Molecular Biology Techniques and Applications
- Protein Degradation and Inhibitors
- Mosquito-borne diseases and control
- Animal Disease Management and Epidemiology
- Single-cell and spatial transcriptomics
Federal Department of Home Affairs
2022-2024
University of Bern
2022-2023
Institute of Virology of the Slovak Academy of Sciences
2023
Friedrich Miescher Institute
2021-2022
University Medical Center Freiburg
2014-2017
University of Freiburg
2016-2017
Institute of Medical Microbiology and Hygiene
2014
Analysis of CD4 + T cell heterogeneity in the lung uncovers a Bcl6-dependent subset that supports mucosal antibody production.
Abstract Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization advanced primary cell culture systems animal models are urgently needed. Here, we characterize recombinant spike gene mutants comparison with VOC Delta well-differentiated human nasal bronchial epithelial cells vitro, followed by vivo fitness hamsters, ferrets hACE2-expressing mice, immunized hACE2-mice. We demonstrate a spike-mediated...
The deacetylase HDAC6 has tandem catalytic domains and a zinc finger domain (ZnF) binding ubiquitin (Ub). While the an antiviral effect, ZnF facilitates influenza A virus (IAV) infection cellular stress responses. By recruiting Ub via ZnF, promotes formation of aggresomes granules (SGs), dynamic structures associated with pathologies such as neurodegeneration. IAV subverts aggresome/HDAC6 pathway to facilitate capsid uncoating during early infection. To target this pathway, we generate...
Approved vaccines are effective against severe COVID-19, but broader immunity is needed new variants and transmission. Therefore, we developed genome-modified live-attenuated (LAV) by recoding the SARS-CoV-2 genome, including 'one-to-stop' (OTS) codons, disabling Nsp1 translational repression removing ORF6, 7ab 8 to boost host immune responses, as well spike polybasic cleavage site optimize safety profile. The resulting OTS-modified LAVs, designated OTS-206 OTS-228, genetically stable can be...
Lysine acetylation is a post-translational modification known to regulate protein functions. Here we identify several sites of the influenza A virus nucleoprotein (NP), including lysine residues K77, K113 and K229. Viral growth mutant encoding K229R, mimicking non-acetylated NP residue, severely impaired compared wildtype or viruses K77R K113R. This attenuation not result decreased polymerase activity, altered expression disordered vRNP co-segregation but rather caused by particle release....
Two novel influenza A-like viral genome sequences have recently been identified in Central and South American fruit bats provisionally designated "HL17NL10" "HL18NL11." All efforts to isolate infectious virus from or generate these viruses by reverse genetics failed date. Recombinant vesicular stomatitis (VSV) encoding the hemagglutinin-like envelope glycoproteins HL17 HL18 place of VSV glycoprotein were generated identify cell lines that are susceptible bat entry. More than 30 derived...
Abstract Packaging of the eight genomic RNA segments influenza A viruses (IAV) into viral particles is coordinated by segment-specific packaging sequences. How signals regulate specific incorporation each segment virions and whether other or host factors are involved in this process unknown. Here, we show that distinct amino acids nucleoprotein (NP) required for segments. This was determined studying NP a bat A-like virus, HL17NL10, context conventional IAV (SC35M). Replacement conserved...
Spatial transcriptomics technologies currently lack scalable and cost-effective options to profile tissues in three dimensions. Technological advances microcomputed tomography enabled non-destructive volumetric imaging of tissue blocks with sub-micron resolution at a centimetre scale. Here, we present X-Pression, deep convolutional neural network-based framework designed reconstruct 3D expression signatures cellular niches from data. By training on singular 2D section paired spatial...
Abstract Variant of concern (VOC) Omicron-BA1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization Omicron-BA.1 advanced primary cell culture systems multiple animal models is urgently needed. Here, we characterized recombinant spike gene mutants comparison with VOC Delta well-differentiated human nasal bronchial epithelial cells vitro, followed by vivo fitness naïve hamsters, ferrets hACE2-expressing mice, immunized hACE2-mice. We...
<title>Abstract</title> Vaccines are the most effective measure against COVID-19. However, novel and highly efficacious vaccines with simplified administration broad immunogenicity, providing systemic mucosal immunity needed. Here, we show development of live-attenuated (LAV) based on (i) recoding SARS-CoV-2 genome to enrich for "one-to-stop" (OTS) codons, (ii) facilitating host responses by disabling non-structural-protein-1 (Nsp1) mediated translational repression, deletion open reading...
The deacetylase HDAC6 has tandem catalytic domains and a zinc finger (ZnF) domain binding ubiquitin (Ub). While the an antiviral effect, ZnF facilitates influenza A virus (IAV) infection cellular stress responses. By recruiting unanchored Ub via its domain, promotes formation of aggresomes granules (SGs), dynamic structures associated with pathologies such as neurodegeneration. IAV subverts aggresome/HDAC6 pathway to facilitate capsid uncoating during early infection. To interfere this...