A5064734663- Influenza Virus Research Studies
- Respiratory viral infections research
- interferon and immune responses
- Animal Disease Management and Epidemiology
- Viral gastroenteritis research and epidemiology
- X-ray Diffraction in Crystallography
- COVID-19 Clinical Research Studies
- Crystallization and Solubility Studies
- Immune Response and Inflammation
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Neonatal Respiratory Health Research
- SARS-CoV-2 and COVID-19 Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Animal Virus Infections Studies
- Virology and Viral Diseases
- Stress Responses and Cortisol
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- COVID-19 Impact on Reproduction
- Congenital Diaphragmatic Hernia Studies
- Parasite Biology and Host Interactions
- RNA modifications and cancer
- Respiratory Support and Mechanisms
University of Veterinary Medicine Hannover, Foundation
2018-2025
Leibniz Institute of Virology (LIV)
2015-2024
German Center for Infection Research
2018-2023
Leibniz Association
2014-2022
Leibniz Institute of Freshwater Ecology and Inland Fisheries
2019
University of Potsdam
2019
Leibniz Institute for Zoo and Wildlife Research
2019
Freie Universität Berlin
2019
University of Lübeck
2015-2018
University of Veterinary Medicine
2018
Mammalian influenza viruses are descendants of avian strains that crossed the species barrier and underwent further adaptation. Since 1997 in southeast Asia, H5N1 highly pathogenic have been causing severe, even fatal disease humans. Although no lineages this subtype established until now, such repeated events may initiate a new pandemic. As model transmission, we used virus SC35 (H7N7), which is low-pathogenic for mice, its lethal mouse-adapted descendant SC35M . Specific mutations...
We have previously reported that mutations in the polymerase proteins PB1, PB2, PA, and nucleocapsid protein NP resulting enhanced transcription replication activities mammalian cells are responsible for conversion of avian influenza virus SC35 (H7N7) into mouse-adapted variant SC35M. show now adaptive D701N PB2 N319K enhance binding these to importin alpha1 cells. Enhanced was paralleled by transient nuclear accumulation cytoplasmic depletion as well increased transport nucleus In cells,...
Influenza A viruses are a threat to humans due their ability cross species barriers, as illustrated by the 2009 H1N1v pandemic and sporadic H5N1 transmissions. Interspecies transmission requires adaptation of viral polymerase importin-α, cellular protein that mediates transport into nucleus where transcription replication genome takes place. In this study, we analysed replication, host specificity pathogenicity avian mammalian influenza viruses, in importin-α-silenced cells...
Neurological symptoms such as cognitive decline and depression contribute substantially to post-COVID-19 syndrome, defined lasting several weeks after initial SARS-CoV-2 infection. The pathogenesis is still elusive, which hampers appropriate treatment. Neuroinflammatory responses neurodegenerative processes may occur in absence of overt neuroinvasion.Here we determined whether intranasal infection male female syrian golden hamsters results persistent brain pathology. Brains 3 (symptomatic)...
ABSTRACT Cleavage of the hemagglutinin (HA) by host proteases is essential for infectivity influenza viruses. Here, we analyzed role serine protease TMPRSS2, which activates HA in human respiratory tract, pathogenesis a mouse model. Replication H7N9 isolate A/Anhui/1/13 and H1N1 H3N2 viruses was compared TMPRSS2 knockout ( −/− ) wild-type (WT) mice. Knockout expression inhibited virus replication explants murine tracheas, bronchi, lungs. also strongly suppressed airway mice, while only...
Mutation D701N in the PB2 protein is known to play a prominent role adaptation of avian influenza A viruses mammalian hosts. In contrast, little about nearby mutations S714I and S714R, which have been observed some highly pathogenic for mammals. We generated recombinant H5N1 with displaying signature 701D or 701N serine, isoleucine, arginine at position 714 compared them polymerase activity virus growth cells, as well pathogenicity mice. led an increase replication efficiency cells mouse...
Influenza A viruses may cross species barriers and transmit to humans with the potential cause pandemics. Interplay of human- (PB2 627K) avian-like 627E) influenza polymerase complexes unknown host factors have been postulated play a key role in interspecies transmission. Here, we identified human importin-α isoforms (α1 α7) as positive regulators but not activity. Human-like activity correlated efficient recruitment α1 α7 viral ribonucleoprotein (vRNPs) without affecting subcellular...
SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified small-molecule library of 34 430 protein kinase inhibitors that were capable inhibiting cytopathic effect in human epithelial cells. These drug are various stages clinical trials. detected key proteins involved cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, DNA-damage response critical for infection. A drug-protein interaction-based...
The mechanism by which ZIKV causes a range of neurological complications, especially congenital microcephaly, is not well understood. fact that microcephaly associated with Asian lineage strains raises the question why this was discovered earlier. One possible explanation and African differ in their abilities to infect cells CNS cause neurodevelopmental problems. Here, we show induce cell death human neural progenitor cells—which are important target development microcephaly—less efficiently...
Summary Males develop more severe SARS-CoV-2 infection related disease outcome than females. Herein, sex hormones were repeatedly proposed to play an important role in Covid-19 pathophysiology and immunity. However, it is yet unclear whether are associated with males In this study, we analyzed hormones, cytokine chemokine responses as well performed a large profile analysis of 600 metabolites critically-ill male female patients comparison healthy controls coronary heart diseases prime...
Abstract COVID-19 survivors often suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Current evidence suggests dysregulated alveolar regeneration as a possible explanation for respiratory PASC, which deserves further investigation in suitable animal model. This study investigates morphological, phenotypical and transcriptomic features infected Syrian golden hamsters. We demonstrate that CK8 + differentiation intermediate (ADI) cells occur following SARS-CoV-2-induced diffuse...
As recently shown, mutations in the polymerase genes causing increased activity mammalian cells are responsible for adaptation of highly pathogenic avian influenza virus SC35 (H7N7) to mice (G. Gabriel et al., Proc. Natl. Acad. Sci. USA 102:18590-18595, 2005). We have now compared mRNA, cRNA, and viral RNA levels its mouse-adapted variant SC35M cells. The increase transcription replication was linked a decrease Thus, efficiency is determinant both host specificity pathogenicity.
Influenza A virus (IAV), a major airborne pathogen, is closely associated with significant morbidity and mortality. The primary target for influenza replication the respiratory epithelium, which reacts to infection by mounting multifaceted antiviral response. part of this mucosal host defense generation reactive oxygen species (ROS) NADPH oxidases. Duox1 Duox2 are main ROS-producing enzymes in airway but their contribution mammalian still ill defined.To gain better understanding Duox...
The impact of the Zika virus (ZIKV) epidemic highlights need for vaccines that reduce or prevent infection and reliably teratogenic complications. live-attenuated measles (MV) vaccine strains are a promising platform, since they induce robust humoral cellular immune responses against additional antigens have an excellent safety record. To explore its potential to protect ZIKV, we compared recombinant Schwarz strain MV encodes ZIKV prM soluble E proteins (MV-Zika-sE) with prototypic...
Helminth parasites infect more than a quarter of the human population and inflict significant changes to immunological status their hosts. Here, we analyze impact helminth infections on efficacy vaccinations using Litomosoides sigmodontis-infected mice. Concurrent infection reduces quantity quality antibody responses vaccination against seasonal influenza. Vaccination-induced protection challenge with pathogenic 2009 pandemic H1N1 influenza A virus is drastically impaired in...
Genome delivery to the proper cellular compartment for transcription and replication is a primary goal of viruses. However, methods analyzing viral genome localization differentiating genomes with high identity are lacking, making it difficult investigate entry-related processes co-examine heterogeneous RNA populations. Here, we present an labeling approach single-cell analysis co-infection dynamics in situ, which uses versatility padlock probes. We applied this method identify influenza A...
Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs pathogenesis are needed. SARS-CoV-2 infection causes interstitial pneumonia varying severity humans models. Pulmonary well peripheral vascular lesions represent a severe, sometimes fatal, disease complication unknown patients. Furthermore, neutrophil (NETs), which known contribute vessel inflammation or...
Vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leading to breakdown the vascular barrier and subsequent edema formation. The aim this study was provide detailed characterization alterations during SARS-CoV-2 evaluate impaired integrity. Groups ten golden Syrian hamsters were infected intranasally with or phosphate-buffered saline (mock infection). Necropsies performed at 1, 3, 6, 14 days post-infection (dpi). Lung...
Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of epithelium and compromises mucociliary clearance, thereby facilitating spread lungs paving way for secondary infections. A detailed understanding mechanism involved in ciliary loss subsequent regeneration is crucial assess possible long-term consequences COVID-19. The aim this study was characterize sequence histological ultrastructural changes observed during after infection golden Syrian hamster model. We...
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an ongoing pandemic with millions of deaths worldwide. Infection humans can be asymptomatic or result fever, fatigue, dry cough, dyspnea, and distress multiorgan failure cases. The pathogenesis COVID-19 is not fully understood, various models employing different species are currently applied. Ferrets infected SARS-CoV-2 efficiently transmit the virus to contact animals. In...
Viruses take advantage of host posttranslational modifications for their own benefit. It was recently reported that influenza A virus proteins interact extensively with the sumoylation system. Thereby, several viral proteins, including NS1 and M1, are sumoylated to facilitate replication. However, what extent is exploited by not fully understood. In this study, we found nucleoprotein (NP) a bona fide target in both NP-transfected cells virus-infected cells. We further NP at two most...
Viral diseases remain serious threats to public health because of the shortage effective means control. To combat surge viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced premature death cells infected with different RNA or DNA viruses, whereas, at same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited replication and spread....