Arthur Wickenhagen
A5079613549- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- Influenza Virus Research Studies
- Hepatitis C virus research
- Respiratory viral infections research
- Virology and Viral Diseases
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- COVID-19 Clinical Research Studies
- Animal Disease Management and Epidemiology
- Immune Cell Function and Interaction
- Hepatitis Viruses Studies and Epidemiology
- Herpesvirus Infections and Treatments
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- HIV Research and Treatment
- Cytomegalovirus and herpesvirus research
- vaccines and immunoinformatics approaches
- Hepatitis B Virus Studies
- Listeria monocytogenes in Food Safety
- HIV/AIDS drug development and treatment
National Institute of Allergy and Infectious Diseases
2024-2025
National Institutes of Health
2024-2025
MRC University of Glasgow Centre for Virus Research
2018-2023
Norwegian University of Science and Technology
2023
Medical Research Council
2021
Radboud University Nijmegen
2017
Radboud University Medical Center
2017
Radboud Institute for Molecular Life Sciences
2017
<h2>Summary</h2> SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines antibody therapeutics. Here, we demonstrate that the immunodominant spike (S) receptor binding motif (RBM) is a highly variable region S provide epidemiological, clinical, molecular characterization prevalent, sentinel RBM mutation, N439K. We N439K protein has enhanced affinity to hACE2 receptor, viruses have similar <i>in vitro</i> replication fitness cause infections clinical...
Abstract Genome sequencing has been widely deployed to study the evolution of SARS-CoV-2 with more than 90,000 genome sequences uploaded GISAID database. We published a method for ( https://www.protocols.io/view/ncov-2019-sequencing-protocol-bbmuik6w ) online on January 22, 2020. This approach rapidly become most popular due its simplicity and cost-effectiveness. Here we present improvements original protocol: i) an updated primer scheme 22 additional primers improve coverage, ii)...
The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention SARS-CoV-2, meaning there is an urgent need for tools that can be used in unaccustomed working with coronaviruses. Here we report range SARS-CoV-2 research. First, describe facile single plasmid reverse...
Inherited genetic factors can influence the severity of COVID-19, but molecular explanation underpinning a association is often unclear. Intracellular antiviral defenses inhibit replication viruses and reduce disease severity. To better understand relevant to we used interferon-stimulated gene (ISG) expression screening reveal that 2′-5′-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show common...
Remdesivir (RDV), a broadly acting nucleoside analogue, is the only FDA approved small molecule antiviral for treatment of COVID-19 patients. To date, there are no reports identifying SARS-CoV-2 RDV resistance in patients, animal models or vitro. Here, we selected drug-resistant viral populations by serially passaging vitro presence RDV. Using high throughput sequencing, identified single mutation RNA-dependent RNA polymerase (NSP12) at residue conserved among all coronaviruses two...
SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that immunodominant spike (S) receptor binding motif (RBM) is most divergent region S, provide epidemiological, clinical, molecular characterization a prevalent RBM variant, N439K. We N439K S protein has enhanced affinity hACE2 receptor, virus similar clinical outcomes in vitro replication fitness as compared wild- type. observed mutation resulted...
Bunyaviruses pose a significant threat to human health, prosperity, and food security. In response viral infections, interferons (IFNs) upregulate the expression of hundreds interferon-stimulated genes (ISGs), whose cumulative action can potently inhibit replication bunyaviruses. We used flow cytometry-based method screen ability ∼500 unique ISGs from humans rhesus macaques Bunyamwera orthobunyavirus (BUNV), prototype both Peribunyaviridae family Bunyavirales order. Candidates possessing...
The genomes of RNA and small DNA viruses vertebrates display significant suppression CpG dinucleotide frequencies. Artificially increasing frequencies results in substantial attenuation virus replication, suggesting that these compositional changes may facilitate recognition non-self sequences. Recently, the interferon inducible protein ZAP, was identified as host factor responsible for sensing viral RNA, through direct binding possibly downstream targeting degradation. Using an arrayed...
Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy while sparing the mRNAs that encode antiviral effectors. Here, we show highly upregulated interferon-stimulated genes (ISGs), which proteins, have distinctive nucleotide compositions. We propose self-targeting by effectors has selected ISG transcripts occupy less self-targeted sequence space. Following interferon (IFN) stimulation, CpG-targeting effector...
Abstract The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion pre-existing immunity and decreased disease severity. Continuous evolution within raised concerns potential increased transmissibility and/or To address this, we evaluate fitness pathogenesis contemporary variants XBB.1.5, XBB.1.16, EG.5.1, JN.1 upper (URT) lower respiratory tract (LRT). We compare vivo infection Syrian...
Interferons (IFN) are cytokines that regulate the expression of hundreds genes during viral infections to generate a broadly antiviral environment in stimulated cell. Antiviral breadth is provided by concurrent many individual IFN-stimulated (ISG), each encoding protein with often exquisite specificity. can also be encoded at single genetic loci ISG products detect molecular feature common diverse types viruses, such as RNA or lipid envelope. Here, we show mechanistic plasticity locus novel...
We measured stability of infectious influenza A(H5N1) virus in irradiated raw milk and wastewater on surfaces. found a relatively slow decay milk, indicating that contaminated fomites pose transmission risks. Although the risk is low, our results call for caution handling disposal from infected cattle.
Abstract Ebola virus (EBOV) and Marburg (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an isolate has been found any sampled. Here, we model filovirus infection the Jamaican fruit bat (JFB), Artibeus jamaicensis, by inoculation with either or MARV through combination of oral, intranasal, subcutaneous routes. Infection results systemic replication oral shedding infectious...
Rapid influenza diagnostic tests (RIDTs) could be useful in the current bovine H5N1 outbreak. Here, we evaluated three RIDTs with H5N1. The RDITs showed comparable sensitivity compared to seasonal A virus H3N2, and no difference was observed between raw milk PBS control.
Abstract Remdesivir (RDV) is used widely for COVID-19 patients despite varying results in recent clinical trials. Here, we show how serially passaging SARS-CoV-2 vitro the presence of RDV selected drug-resistant viral populations. We determined that E802D mutation RNA-dependent RNA polymerase was sufficient to confer decreased sensitivity without affecting fitness. Analysis more than 200,000 sequences globally circulating variants no evidence widespread transmission RDV-resistant mutants....
Interferon gamma (IFN-γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to site of RSV infection, but it is unclear whether cell-cell interactions between monocytes regulate IFN-γ production. In this study, micro-array data identified upregulation sialic acid-binding immunoglobulin-type lectin 1 (Siglec-1) human RSV-infected infants. vitro, increased expression Siglec-1 on healthy newborn adult...
Summary Ebola virus (EBOV) and Marburg (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Bat species both Chiropteran suborders host filoviruses, suggesting bats may have coevolved with this viral family. Correlative data implicate as natural EBOV hosts, but neither a full-length genome nor an isolate has been found any sampled. Here, we modelled filovirus infection the Jamaican fruit bat (JFB), Artibeus jamaicensis . Bats were inoculated either or MARV through...
The prenylated form of the human 2′-5′-oligoadenylate synthetase 1 (OAS1) protein has been shown to potently inhibit replication Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), virus responsible for Disease 2019 (COVID-19) pandemic. However, OAS1 orthologue in horseshoe bats (superfamily Rhinolophoidea), reservoir host SARS-related coronaviruses (SARSr-CoVs), lost prenylation signal required this antiviral activity. Herein, we used an ancestral state reconstruction approach...
The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion pre-existing immunity and decreased disease severity. Continuous evolution within raised concerns potential increased transmissibility and/or To address this, we evaluated fitness pathogenesis contemporary variants XBB.1.5, XBB.1.16, EG.5.1, JN.1 upper (URT) lower respiratory tract (LRT). We compared vivo infection Syrian hamsters...
Abstract The ancestral sarbecovirus giving rise to SARS-CoV-2 is posited have originated in bats. While causes asymptomatic severe respiratory disease humans, little known about the biology, virus tropism, and immunity of SARS-CoV-2-like sarbecoviruses has been shown infect multiple mammalian species, including various rodent non-human primates, Egyptian fruit We show that can utilize Jamaican bat ( Artibeus jamaicensis) ACE2 spike for entry vitro. Therefore, we investigate as a possible...
Human metapneumovirus (HMPV) is a pneumovirus that may cause severe respiratory disease in humans. HMPV infection has been found to increase susceptibility bacterial superinfections leading increased morbidity and mortality. The molecular mechanisms underlying HMPV-mediated are poorly understood largely understudied. Type I interferons (IFNs), while critical for antiviral defenses, often have detrimental effects by skewing the host immune response cytokine output of cells. It currently...
Abstract Cross-species transmission of avian influenza A viruses (IAVs) into humans could represent the first step a future pandemic 1 . Multiple factors limiting spillover and adaptation IAVs in have been identified, but they are not sufficient to explain which virus lineages more likely cross species barrier 1,2 Here, we identified human BTN3A3 3 (butyrophilin subfamily member A3) as potent inhibitor IAVs. We determined that is constitutively expressed airways its antiviral activity...