- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Toxoplasma gondii Research Studies
- Reproductive System and Pregnancy
- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- HIV Research and Treatment
- Animal Virus Infections Studies
- IL-33, ST2, and ILC Pathways
- Viral Infections and Vectors
- CAR-T cell therapy research
- MicroRNA in disease regulation
- RNA regulation and disease
- Immune cells in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Parvovirus B19 Infection Studies
- Long-Term Effects of COVID-19
- Animal Disease Management and Epidemiology
University of Rijeka
2015-2024
Institut Pasteur
2009
Ludwig-Maximilians-Universität München
1998
Mouse strains are either resistant or susceptible to murine cytomegalovirus (MCMV). Resistance is determined by the Cmv1(r) (Ly49h) gene, which encodes Ly49H NK cell activation receptor. The protein encoded m157 gene of MCMV has been defined as a ligand for Ly49H. To find out whether only MCMV, we constructed deletion mutant and revertant virus. Viruses were tested susceptibility control in Ly49H+ Ly49H- mouse strains. Deletion abolished viral cells, resulting higher virus virulence vivo....
Reactivation from latent cytomegalovirus (CMV) infection is often associated with conditions of immunosuppression and can result in fatal disease. Whether the maintenance systemic CMV latency mainly governed by factors infected cell or immune control functions unknown. Likewise, putative mechanisms which could prevent induction spread recurrent are not clearly identified. We took advantage latently B cell-deficient mice a sensitive method for virus detection to study reactivation after...
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...
Article29 January 2019Open Access Source DataTransparent process The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-κB signaling STING's dual role during MCMV infection Markus Stempel orcid.org/0000-0002-9240-3987 Viral Immune Modulation Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany Search more papers by this author Baca Chan Vanda Juranić Lisnić Center Proteomics, Faculty Medicine, University Rijeka, Croatia Astrid...
The NK cell–activating receptor NKG2D interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (MCMV). We set out to define the viral gene product regulating murine UL16-binding protein-like transcript (MULT)-1, a newly described ligand. show that MCMV infection strongly induces MULT-1 expression, but surface expression this glycoprotein is nevertheless completely abolished virus. Screening panel deletion mutants defined m145 as regulator MULT-1....
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...
Natural killer (NK) cells and CD8(+) T play a prominent role in the clearance of mouse cytomegalovirus (MCMV) infection. The NK modulating T-cell response to MCMV infection is still subject intensive research. For analyzing impact on mounting contribution these virus control during first days postinfection (p.i.), we used C57BL/6 mice which are specifically activated through Ly49H receptor engaged by MCMV-encoded ligand m157. Our results indicate that requirement for early inversely...
Cytomegaloviruses encode numerous functions that inhibit antigen presentation in the major histocompatibility complex (MHC) class I pathway vitro. One example is mouse cytomegalovirus (MCMV) glycoprotein gp40, encoded by m152 gene, which selectively retains murine but not human MHC complexes endoplasmic reticulum-Golgi intermediate compartment/cis-Golgi compartment (Ziegler, H., R. Thäle, P. Lucin, W. Muranyi, T. Flohr, H. Hengel, Farrell, Rawlinson, and U.H. Koszinowski. 1997. Immunity....
Both human and mouse cytomegaloviruses (CMVs) encode proteins that inhibit the activation of NK cells by down-regulating cellular ligands for activating cell receptor NKG2D. Up to now, three NKG2D receptor, named RAE-1, H60, MULT-1, have been identified in mice. The resistance strains murine CMV (MCMV) infection is determined their ability generate an effective response. MCMV gene m152, a member m145 family, down-regulates expression RAE-1 order avoid control vivo. Here we report m155 gene,...
Members of the α- and β-subfamily herpesviridae encode glycoproteins that specifically bind to Fc part immunoglobulin (Ig)G. Plasma membrane resident herpesviral receptors seem prevent virus-specific IgG from activating antibody-dependent effector functions. We show mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 H60 cell surface. Deletion m138/fcr-1 gene MCMV genome attenuates viral replication...
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...
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...
Regulatory T (Treg) cells dampen an exaggerated immune response to viral infections in order avoid immunopathology. Cytomegaloviruses (CMVs) are herpesviruses usually causing asymptomatic infection immunocompetent hosts and induce strong cellular immunity which provides protection against CMV disease. It remains unclear how these persistent viruses manage induction of immunopathology not only during the acute but also life-long persistence virus reactivation. This may be due numerous...
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...