A5059250031- Hepatitis B Virus Studies
- Hepatitis C virus research
- Immunotherapy and Immune Responses
- Liver Disease Diagnosis and Treatment
- Immune Cell Function and Interaction
- Viral gastroenteritis research and epidemiology
- Immune Response and Inflammation
- Diabetes and associated disorders
- T-cell and B-cell Immunology
- Viral Infections and Outbreaks Research
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- interferon and immune responses
- Immune cells in cancer
- Virus-based gene therapy research
- Hepatitis Viruses Studies and Epidemiology
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Animal Virus Infections Studies
- Cytokine Signaling Pathways and Interactions
- Viral Infections and Vectors
- CAR-T cell therapy research
- Pancreatic function and diabetes
- Liver Disease and Transplantation
- Cancer Immunotherapy and Biomarkers
Vita-Salute San Raffaele University
2015-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2015-2025
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2015-2025
San Raffaele University of Rome
2015-2017
Scripps Research Institute
2004-2016
IRCCS Ospedale San Raffaele
1994-2015
German Rheumatism Research Centre
2009
University Hospital of Zurich
2009
Salk Institute for Biological Studies
2007
Karolinska University Hospital
2004
Viral clearance during hepatitis B virus (HBV) infection has been thought to reflect the destruction of infected hepatocytes by CD8 + T lymphocytes. However, in this study, HBV DNA was shown largely disappear from liver and blood acutely chimpanzees long before peak cell infiltration most disease. These results demonstrate that noncytopathic antiviral mechanisms contribute viral acute purging replicative intermediates cytoplasm covalently closed circular nucleus cells.
Hepatitis B virus (HBV) transgenic mice whose hepatocytes replicate the at levels comparable to that in infected livers of patients with chronic hepatitis have been produced, without any evidence cytopathology. High-level viral gene expression was obtained liver and kidney tissues three independent lineages. These animals were produced a terminally redundant DNA construct (HBV 1.3) starts just upstream HBV enhancer I, extends completely around circular genome, ends downstream unique...
We have previously reported that hepatitis B virus (HBV)–specific CD8+ cytotoxic T lymphocytes and CD4+ helper can inhibit HBV replication in the liver of transgenic mice by secreting interferon (IFN)-γ when they recognize viral antigen. To determine whether an activated innate immune system also replication, this study we natural killer (NKT) cells a single injection α-galactosylceramide (α-GalCer), glycolipid antigen presented to Vα14+NK1.1+ nonclassical major histocompatibility complex...
The molecular and cellular mechanisms responsible for cytotoxic T lymphocyte (CTL)-induced immunopathology are not well defined. Using a model in which hepatitis B surface antigen (HBsAg)-specific CTL cause an acute necroinflammatory liver disease HBsAg transgenic mice, we demonstrate that class I-restricted pathogenesis is orderly, multistep process involves direct as indirect consequences of activation. It begins (step 1) almost immediately antigen-specific CTL-target cell interaction...
During hepatitis B virus (HBV) infection, distinct host-virus interactions may establish the patterns of viral clearance and persistence extent virus-associated pathology. It is generally thought that HBV-specific class I-restricted cytotoxic T lymphocytes (CTLs) play a critical role in this process by destroying infected hepatocytes. This cytopathic mechanism, however, could be lethal if most hepatocytes are infected. In current study, we demonstrate CTLs profoundly suppress hepatocellular...
Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis HBV-associated HCC involves both viral and host factors. latter include functionally inefficient CD8 + T-cell response that fails to clear from liver but sustains chronic necroinflammatory process contributes HCC. According this scenario, amelioration immune-mediated injury may prevent Because platelets facilitate by promoting hepatic accumulation...
Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive recognizing hepatocellular driven into state immune dysfunction, identify subset (referred as KC2)...
The development of a tractable small animal model faithfully reproducing human coronavirus disease 2019 pathogenesis would arguably meet pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the ACE2 epithelial cells (K18-hACE2 mice) that are intranasally instilled with liquid severe acute respiratory syndrome 2 (SARS-CoV-2) suspension under deep anesthesia. Unfortunately, this experimental approach results disproportionate high central...
Abstract Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under presumption that it is primary defense mechanism following vaccination or infection. This perspective, however, can overlook role of T cells, particularly when levels are low absent. Here we show, through studies in mouse models...
Hepatocellular carcinoma (HCC) is a common complication of chronic hepatitis B virus (HBV) infection. The pathogenetic mechanisms potentially responsible for HCC during HBV infection are not well defined. This study demonstrates that immune-mediated liver cell injury triggers the development in absence viral transactivation, insertional mutagenesis, and genotoxic chemicals. These results strongly suggest immune response to both necessary sufficient cause cancer infection, all other...
We have previously shown that hepatitis B virus (HBV) replication is inhibited noncytopathically in the livers of transgenic mice following injection HBV-specific cytotoxic T lymphocytes (CTLs) or infection with unrelated hepatotropic viruses, including lymphocytic choriomeningitis (LCMV) and adenovirus. These effects are mediated by gamma interferon (IFNgamma), tumor necrosis factor alpha (TNFalpha), IFNalpha/beta. In present study, we crossed HBV genetically deficient for IFNgamma...
Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting cells that has the ability to induce gamma interferon (IFN-gamma) secretion T and natural killer generate normal Th1 responses. These properties suggest IL-12 may play an important role in immune response many viruses, including hepatitis B virus (HBV). Recently, we have shown HBV-specific cytotoxic lymphocytes inhibit HBV replication livers of transgenic mice noncytolytic process mediated part IFN-gamma. In...
A unique characteristic of the hepatitis B virus is production a secreted form (precore or HBeAg) structural nucleocapsid (core HBcAg). By using T cell receptor (TCR) transgenic (Tg) and TCR x HBc/HBeAg double- triple-Tg pairs, we demonstrate that HBeAg elicits tolerance, whereas HBcAg nontolerogenic in this system. In fact, HBc double-Tg mice spontaneously seroconvert to IgG anti-HBc positivity at an early age. However, presence serum HBe prevents seroconversion. mediates its...