- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Diabetes and associated disorders
- Herpesvirus Infections and Treatments
- RNA Interference and Gene Delivery
- Adipokines, Inflammation, and Metabolic Diseases
- SARS-CoV-2 and COVID-19 Research
- Reproductive System and Pregnancy
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- CAR-T cell therapy research
- Cell death mechanisms and regulation
- Analytical Chemistry and Sensors
- Nanofabrication and Lithography Techniques
- Electron Spin Resonance Studies
- Toxoplasma gondii Research Studies
- Viral Infections and Immunology Research
- Parvovirus B19 Infection Studies
- Immune cells in cancer
- Autism Spectrum Disorder Research
- MicroRNA in disease regulation
- Anodic Oxide Films and Nanostructures
University of Rijeka
2009-2024
German Rheumatism Research Centre
2013-2024
Charité - Universitätsmedizin Berlin
2014-2022
Leibniz Association
2013-2018
Cytomegaloviruses express large amounts of viral miRNAs during lytic infection, yet, they only modestly alter the cellular miRNA profile. The most prominent alteration upon murine cytomegalovirus (MCMV) infection is rapid degradation miR-27a and miR-27b. Here, we report that this regulation mediated by ∼1.7 kb spliced highly abundant MCMV m169 transcript. Specificity to miR-27a/b a single, apparently optimized, binding site located in its 3'-UTR. This easily efficiently retargeted other...
Natural killer (NK) cells are crucial in resistance to certain viral infections, but the mechanisms used recognize infected remain largely unknown. Here, we show that activating Ly49P receptor recognizes with mouse cytomegalovirus (MCMV) by a process requires presence of H2-Dk and MCMV m04 protein. Using H2 chimeras between H2-Db -Dk, demonstrate peptide-binding platform is required for recognition. We identified as component necessary recognition using panel MCMV-deletion mutant viruses...
ABSTRACT Cleavage of human cytomegalovirus (HCMV) genomes as well their packaging into capsids is an enzymatic process mediated by viral proteins and therefore a promising target for antiviral therapy. The HCMV pUL56 pUL89 form the terminase play central role in cleavage-packaging, but several additional proteins, including pUL51, had been suggested to contribute this process, although they remain largely uncharacterized. To study function pUL51 infected cells, we constructed mutants...
Cytomegaloviruses (CMVs) are renowned for interfering with the immune system of their hosts. To sidestep antigen presentation and destruction by CD8+ T cells, these viruses reduce expression major histocompatibility complex class I (MHC I) molecules. However, this process sensitizes virus-infected cells to natural killer (NK) cell–mediated killing via “missing self” axis. Mouse cytomegalovirus (MCMV) uses m152 m06 encoded proteins inhibit surface MHC In addition, it encodes another protein,...
Human CMV (HCMV) is a major cause of morbidity and mortality in both congenitally infected immunocompromised individuals. Development an effective HCMV vaccine would help protect these vulnerable groups. NK group 2, member D (NKG2D) potent activating receptor expressed by cells the innate adaptive immune systems. Its importance surveillance indicated elaborative evasion mechanisms evolved virus to avoid NKG2D. In order study this signaling pathway, we engineered recombinant mouse expressing...
Recognition of mouse cytomegalovirus (MCMV)–infected cells by activating NK cell receptors was first described in the context Ly49H, which confers resistance to C57BL/6 mice. We investigated ability other Ly49 recognize MCMV-infected mice from various H-2 backgrounds. observed that Ly49P1 NOD/Ltj mice, Ly49L BALB and Ly49D2 PWK/Pas respond H-2Dk viral protein m04/gp34. also seen H-2d and/or H-2f contexts, depending on receptor examined, but never H-2b. Furthermore, BALB.K (H-2k) showed...
The poliovirus receptor (PVR) is a ubiquitously expressed glycoprotein involved in cellular adhesion and immune response. It engages the activating DNAX accessory molecule (DNAM)-1, inhibitory TIGIT, CD96 with both functions. Human cytomegalovirus (HCMV) down-regulates PVR expression, but significance of this viral function vivo remains unknown. Here, we demonstrate that mouse CMV (MCMV) also surface PVR. m20.1 protein MCMV retains endoplasmic reticulum promotes its degradation. A mutant...
Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles. Due to virus's restricted host cell type tropism lack tools for VZV proteomics, it one least-characterized human herpesviruses. We generated 251 monoclonal antibodies (MAbs) against 59 71 (83%) currently known unique proteins characterize protein expression in vitro situ. Using this new set MAbs, 44 viral were detected by Western blotting (WB) indirect immunofluorescence (IF); 13 WB only, 2 IF only. A large...
NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes. Despite its established role as potent activator the immune system, NKG2D-driven regulation CD4+ T helper (Th) cell–mediated immunity remains unclear. In this study, we demonstrate that modulates Th1 proinflammatory T-bet+ Th17 cell effector functions in vitro vivo. particular, promotes higher production cytokines by cells reinforces their transcription type 1 signature genes, including Tbx21....
Significance There are a number of pathogens for which the immunity acquired postinfection does not fully protect against reinfection and disease. Therefore, vaccines offering superior protection compared with following natural infection needed. Due to unique pattern immune response induced by cytomegaloviruses (CMVs), live attenuated CMVs attractive candidates vaccine vectors. Here we have demonstrated that recombinant CMV vector expressing RAE-1γ, cellular ligand activating NKG2D receptor...
CMVs efficiently target MHC I molecules to avoid recognition by cytotoxic T cells. However, the lack of on cell surface renders infected susceptible NK killing upon missing self recognition. To counter this, mouse CMV (MCMV) rescues some engage inhibitory Ly49 receptors. Here we identify a new viral protein, MATp1, that is essential for rescue. Rescued altered-self show increased affinity receptors, resulting in inhibition cells despite substantially reduced levels. This enables virus evade...
Natural killer (NK) cells are a subset of innate lymphoid (ILC) capable recognizing stressed and infected through multiple germ line-encoded receptor-ligand interactions. Missing-self recognition involves NK cell sensing the loss host-encoded inhibitory ligands on target cells, including MHC class I (MHC-I) molecules other MHC-I-independent ligands. Mouse cytomegalovirus (MCMV) infection promotes rapid host-mediated NKR-P1B ligand Clr-b (encoded by Clec2d) cells. Here we provide evidence...
Memory CD8 T cells play an important role in the protection against breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether route of antigen exposure impacts these at a functional level is incompletely characterized. Here, we compare memory cell response common SARS-CoV-2 epitope after vaccination, infection, or both. demonstrate comparable capacity when restimulated directly ex vivo, independent antigenic history. However, analysis receptor usage...
<title>Abstract</title> Viral infection makes us feel sick. The extent of these changes to our metabolism are relative the severity disease. Whether blood glucose levels subject infection-induced modulation is largely unknown. Here we show that strong, non-lethal restricts systemic availability which promotes antiviral IFN-I response. Following viral mice, find IFNγ produced by γδ T cells directly stimulates pancreatic β-cells increase glucose-induced insulin release. Subsequently,...