A5052845799- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Herpesvirus Infections and Treatments
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Toxoplasma gondii Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Parvovirus B19 Infection Studies
- SARS-CoV-2 detection and testing
- IL-33, ST2, and ILC Pathways
- Adipokines, Inflammation, and Metabolic Diseases
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Respiratory viral infections research
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- Hematopoietic Stem Cell Transplantation
- Erythrocyte Function and Pathophysiology
- Reproductive System and Pregnancy
University of Rijeka
2016-2025
Cardiff University
2024
Ludwig-Maximilians-Universität München
2013-2018
The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, Omicron variant was discovered and immediately classified as a of concern (VOC), since it shows substantially more mutations in spike protein than any previous variant, especially receptor-binding domain (RBD). We analyzed binding RBD to human angiotensin-converting enzyme-2 receptor (ACE2) ability sera from patients or vaccinees comparison Wuhan, Beta, Delta variants.
Herpesvirus gH/gL envelope glycoprotein complexes are key players in virus entry as ligands for host cell receptors and by promoting fusion of viral envelopes with cellular membranes. Human cytomegalovirus (HCMV) has two alternative complexes, gH/gL/gO gH/gL/UL128,130,131A which both shape the HCMV tropism. By studying binding particles to fibroblasts, we could first time show that virion binds platelet-derived growth factor-α (PDGFR-α) on surface fibroblasts either directly or indirectly...
Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, entry pathways mode of spread virus. For murine (MCMV), serves as a model for HCMV, complex functionally homologous to HCMV has been described. Knock-out MCMV gO does impair, but not abolish, virus indicating that also might form an alternative complex. Here, we show CC chemokine MCK-2 with gH, is incorporated into virion. We could additionally mutants...
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation substantially differs from effects triggered upon injection synthetic agents. In infections, inflammatory responses had to exceed local thresholds within bone...
Abstract This unit describes procedures for infecting newborn and adult mice with murine cytomegalovirus (MCMV). Methods are included propagating MCMV in cell cultures preparing a more virulent form of from salivary glands infected mice. A plaque assay is provided determining titers tissues or virus stocks. Also, method described the embryonic fibroblasts used assay. © 2018 by John Wiley & Sons, Inc.
Herpesviruses form different gH/gL virion envelope glycoprotein complexes that serve as entry for mediating viral cell-type tropism in vitro; their roles vivo, however, remained speculative and can be addressed experimentally only animal models. For murine cytomegalovirus two alternative complexes, gH/gL/gO gH/gL/MCK-2, have been identified. A limitation of studies on vivo has the difficulty distinguishing between infection initiation by into first-hit target cells subsequent cell-to-cell...
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...
Congenital human cytomegalovirus (cHCMV) infection of the brain is associated with a wide range neurocognitive sequelae. Using newborn mice mouse (MCMV) as reliable model that recapitulates many aspects cHCMV infection, including disseminated CNS altered neurodevelopment, and sensorineural hearing loss, we have previously shown mitigation inflammation prevented alterations in cerebellar development, suggesting host inflammatory factors are key drivers neurodevelopmental defects. Here, show...
COVID-19 vaccines prevent severe forms of the disease, but do not warrant complete protection against breakthrough infections. This could be due to suboptimal mucosal immunity at site virus entry, given that all currently approved are administered via intramuscular route. In this study, we assessed humoral and cellular immune responses in BALB/c mice after intranasal immunization with adenoviral vector ChAdOx1-S expressing full-length Spike protein SARS-CoV-2. We showed both routes...
The aim of this study was to characterize the systemic cytokine signature critically ill COVID-19 patients in a high mortality setting aiming identify biomarkers severity, and explore their associations with viral loads clinical characteristics. We studied two patient cohorts from referral centre located Central Europe. were recruited during pre-alpha/alpha (November 2020 April 2021) delta (end period respectively. determined both serum bronchoalveolar SARS-CoV-2 load identified variant...
Abstract Congenital HCMV infection is a leading infectious cause of long‐term neurodevelopmental sequelae. Infection newborn mice with mouse cytomegalovirus (MCMV) intraperitoneally well‐established model congenital human infection, which best recapitulates the hematogenous route virus spread to brain and subsequent pathology. Here, we used this investigate role, dynamics, phenotype CD8 + T cells in following mice. We show that infiltrate form pool tissue‐resident memory (T RM cells) persist...
Significance CD8 + T lymphocytes protect from intracellular pathogens by recognizing pathogen's antigenic peptides presented on MHC-I molecules. Many viruses evade cell control using genes that subvert presentation infected cells. Here we shift this paradigm and show viral proteins block the effector branch of cells are more efficient for evasion than downregulation. The signaling in target at level caspase-8 as a crucial convergence point death-receptor perforine/granzyme pathways cytotoxic...
Abstract To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a β-herpesvirus, persists for the long term and across organs PDGFRα-positive cells, with similar or higher genome loads than previously known sites of cytomegalovirus latency. Whereas gene transcription cells is almost completely silenced at 5 months post-infection, these give rise reactivated virus ex vivo, arguing they support latent infection. Notably,...
The glycoproteins gH and gL of human cytomegalovirus (HCMV) form a complex either with pUL74 (trimeric complex) or proteins the UL128 locus (pentameric complex). While pentameric is dispensable for viral growth in fibroblasts, deletion causes small plaque phenotype HCMV lab strains, accompanied by greatly reduced cell-free infectivity. As isolates, shortly after cultivation from clinical specimens, do not release infectious viruses, we wondered whether would also affect virus this...
All human herpesviruses establish latency following the resolution of primary infection. Among these, α-herpesviruses HSV-1, HSV-2 and VZV in neurons, whereas neurons are not traditionally considered a site for other herpesviruses. Using combination vivo murine models ex fetal tissues, we discovered that cytomegalovirus (CMV), ubiquitous β-herpesvirus, can persist CD4+ T-cell-derived interferon-gamma is critical restricting active viral replication this cell type. Furthermore, show mouse CMV...
Abstract The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, Omicron variant was discovered and classified as a of concern (VOC). shows substantially more mutations in spike protein than any previous variant, mostly receptor binding domain (RBD). We analyzed RBD to human ACE2 (hACE2) ability sera from patients or vaccinees comparison Wuhan, Beta Delta RBDs variants. All were produced insect cells. hACE2 ELISA microscale thermophoresis (MST). Similarly, 27...
This article describes procedures for infecting adult mice with murine cytomegalovirus (MCMV) and newborn to model congenital CMV infection. Methods are included propagating MCMV in cell cultures preparing a more virulent form of from the salivary glands infected mice. A plaque assay is provided determining titers tissues or virus stocks. Also, methods described embryonic fibroblasts used MCMV, assay. © 2022 Wiley Periodicals LLC.
Innate lymphoid cells (ILCs) are largely tissue-resident that participate in the maintenance of tissue homeostasis and react early to inflammatory events. Mature ILCs divided into three major groups based on transcription factors required for their development function. Under physiological conditions, present within choroid plexus meninges while CNS parenchyma is almost devoid these cells. However, pathological conditions such as autoimmune neuroinflammation viral infections result...