A5081595462- Cytomegalovirus and herpesvirus research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- Cytokine Signaling Pathways and Interactions
- T-cell and B-cell Immunology
- Hepatitis B Virus Studies
- Long-Term Effects of COVID-19
- Hepatitis C virus research
- Toxoplasma gondii Research Studies
- Cutaneous Melanoma Detection and Management
- SARS-CoV-2 detection and testing
- CAR-T cell therapy research
- Reproductive System and Pregnancy
- COVID-19 epidemiological studies
- HIV Research and Treatment
- Hematopoietic Stem Cell Transplantation
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Virus-based gene therapy research
- Immune Response and Inflammation
University of Duisburg-Essen
2016-2025
Institute of Virology of the Slovak Academy of Sciences
2022-2024
Huazhong University of Science and Technology
2020-2023
Essen University Hospital
2013-2023
Heinrich Heine University Düsseldorf
2008-2015
Ludwig-Maximilians-Universität München
2013
Addenbrooke's Hospital
2013
University of Edinburgh
2013
Barcelona Biomedical Research Park
2013
Düsseldorf University Hospital
2011
Abstract Long-term antibody responses and neutralizing activities in response to SARS-CoV-2 infection are not yet clear. Here we quantify immunoglobulin M (IgM) G (IgG) antibodies recognizing the receptor-binding domain (RBD) of spike (S) or nucleocapsid (N) protein, during a period 6 months from COVID-19 disease onset 349 symptomatic patients who were among first be infected world-wide. The positivity rate magnitude IgM-S IgG-N increase rapidly. High levels IgM-S/N IgG-S/N at 2-3 weeks...
Abstract Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFNγ secretion CD8 + T cells is critical for therapy efficacy having anti-proliferative and pro-apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of resistance in different melanoma patient models. Chromosomal alterations subsequent inactivating mutations genes the signalling cascade, most often JAK1 or JAK2, protect from anti-tumour activity. JAK1/2 mutants further evolve into...
Abstract Glucose metabolism and innate immunity evolved side-by-side. It is unclear if how the two systems interact with each other during hepatitis B virus (HBV) infections and, so, which mechanisms are involved. Here, we report that HBV activates glycolysis to impede retinoic acid-inducible gene I (RIG-I)-induced interferon production. We demonstrate sequesters MAVS from RIG-I by forming a ternary complex including hexokinase (HK). Using series of pharmacological genetic approaches,...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic has not been very well characterized patients. Here, we analyzed differentiation and profile of cells 30 cases mild during infection. SARS-CoV-2 induced CD8+ cells, CD4+ by simultaneous production granzyme A B as perforin within different effector subsets....
Although all 12 subtypes of human interferon alpha (IFN-α) bind the same receptor, recent results have demonstrated that they elicit unique host responses and display distinct efficacies in control different viral infections. The IFN-α2 subtype is currently HIV-1 clinical trials, but it has not consistently reduced loads patients most effective against vitro We now demonstrate humanized mice that, when delivered at high dose, IFN-α14 very potent anti-HIV-1 activity whereas does not. In both...
Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress host extent which contributes overall pattern of viral replication pathogenesis remains elusive. Here, we combine RNA sequencing ribosomal profiling analyses systematically address question. By simultaneously examining changes in transcription along HCMV infection,...
Major advances have been made in understanding the dynamics of humoral immunity briefly after acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics antibody responses convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 and quantified IgM IgG antibodies recognizing nucleocapsid (N) protein or receptor binding domain (RBD) spike (S). After one year, approximately 90% recovered still...
Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The availability effective and well-tolerated antiviral drugs for treatment COVID-19 patients still very limited. Traditional herbal medicines elicit activity against various viruses might therefore represent a promising option complementary patients. application turmeric root in medicine has long history. Its bioactive ingredient curcumin shows broad-spectrum...
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) affected over 120 million people and killed 2.7 individuals March 2021. While intermediate interactions between SARS-CoV-2 immune system have been studied extensively, long-term impacts on cellular remain to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells 49 COVID-19-convalescent (CI) comparison 27 matched...
Significance Type I interferons (IFN-I) exhibit various biological effects during viral infections, and they have been successfully used for clinical treatment of diseases. Humans express 12 IFNα subtypes, which strongly differ in their antiviral responses against different viruses. Here we analyzed the activity all human subtypes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to identify underlying immune signatures explore therapeutic potential. Our data provide a systemic...
A mouse cytomegalovirus (MCMV) gene conferring interferon (IFN) resistance was identified. This gene, M27, encodes a 79-kD protein that selectively binds and down-regulates for signal transducer activator of transcription (STAT)-2, but it has no effect on STAT1 activation signaling. The absence pM27 conferred MCMV susceptibility to type I IFNs (α/β), had much more dramatic II (γ) in vitro vivo. comparative analysis M27+ M27− revealed the antiviral efficiency IFN-γ partially dependent...
Human cytomegalovirus is a ubiquitous herpesvirus that establishes lifelong latent infection. Changes in immune homeostasis induce the reactivation of lytic infection, which mostly inapparent healthy individuals but often causes overt disease immunocompromised hosts. Based on discrepant tumor necrosis factor receptor 1 surface disposition between human AD169 variants differing ULb' region, we identified latency-associated gene product pUL138, also expressed during productive as selective...
Human cytomegalovirus (HCMV) establishes lifelong infection with recurrent episodes of virus production and shedding despite the presence adaptive immunological memory responses including HCMV immune immunoglobulin G (IgG). Very little is known how evades from humoral cellular IgG-dependent responses, latter being executed by cells expressing surface receptors for Fc domain IgG (FcγRs). Remarkably, expresses RL11-encoded gp34 UL119-118-encoded gp68 type I transmembrane glycoproteins which...
Innate immune activation is essential to mount an effective antiviral response and prime adaptive immunity. Although a crucial role of CD169+ cells during vesicular stomatitis virus (VSV) infections increasingly recognized, factors regulating viral remain unclear. Here, we show that tumor necrosis factor produced by CD11b+ Ly6C+ Ly6G+ following infection with VSV. The absence TNF or receptor 1 (TNFR1) resulted in reduced numbers type I interferon (IFN-I) production VSV infection, severe...
Abstract Long-term antibody responses and neutralizing activities following SARS-CoV-2 infections have not yet been elucidated. We quantified immunoglobulin M (IgM) G (IgG) antibodies recognizing the receptor-binding domain (RBD) of spike (S) or nucleocapsid (N) protein, during a period six months COVID-19 disease onset in 349 symptomatic patients, which were among first world-wide being infected. The positivity rate magnitude IgM-S IgG-N increased rapidly. High levels IgM-S/N IgG-S/N at 2-3...
While the immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID‐19) has been characterized in several well-conducted clinical trials, real-world evidence concerning immune responses severe acute respiratory syndrome 2 (SARS‐CoV‐2) raised by such is currently missing. Here, we comprehensively various parameters SARS-CoV-2-specific cellular and humoral induced COVID-19 126 individuals under conditions. After two doses vaccination, S-receptor binding domain IgG (S-RBD...
Understanding tumor resistance to T cell immunotherapies is critical improve patient outcomes. Our study revealed a role for transcriptional suppression of the tumor-intrinsic HLA class I (HLA-I) antigen processing and presentation machinery (APM) in therapy resistance. Low HLA-I APM mRNA levels melanoma metastases before immune checkpoint blockade (ICB) correlated with nonresponsiveness poor clinical outcome. Patient-derived cells silenced escaped recognition by autologous CD8+ cells....
We have investigated the role of signal transducer and activator transcription (STAT) 2 during human cytomegalovirus (HCMV) replication found that protein levels STAT2 are downregulated. downregulation was observed in HCMV clinical isolates laboratory strains with exception strain Towne. The HCMV-induced loss occurred despite an increased accumulation mRNA; it required early gene expression. decrease sensitive to proteasome inhibition, suggesting degradation via ubiquitin pathway. Notably,...
We have previously shown that Toll-like receptor (TLR) agonists contribute to the control of viral infection by augmenting virus-specific CD8(+) T-cell responses. It is also well established signaling TLRs results in production pro-inflammatory cytokines such as interleukin 6 (IL-6). However, how these influence response during TLR agonist stimulation remained largely unknown. Here, we investigated role TLR-induced IL-6 shaping responses Friend retrovirus (FV) mouse model. show induced...
Interferons (IFNs) are pleotropic cytokines secreted upon encounter of pathogens and tumors. Applying their antipathogenic, antiproliferative immune stimulatory capacities, recombinant IFNs frequently prescribed as drugs to treat different diseases. act by changing the gene expression profile cells. Due characteristics like rapid induction signaling, also represent prototypical model systems for various aspects biomedical research (e.g. signal transduction). In regard signaling activated...