A5100396626- interferon and immune responses
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Viral Infections and Immunology Research
- Viral Infections and Vectors
- Immune Response and Inflammation
- Systemic Lupus Erythematosus Research
- Cancer-related molecular mechanisms research
- Animal Virus Infections Studies
- Hepatitis Viruses Studies and Epidemiology
- Immune Cell Function and Interaction
- Animal Disease Management and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- Animal Nutrition and Physiology
- Virus-based gene therapy research
- Liver Disease Diagnosis and Treatment
- Influenza Virus Research Studies
- Viral gastroenteritis research and epidemiology
- Animal Genetics and Reproduction
- Cell Adhesion Molecules Research
- Muscle Physiology and Disorders
- Genetic and phenotypic traits in livestock
- MicroRNA in disease regulation
- Mosquito-borne diseases and control
- RNA regulation and disease
Agricultural Genomics Institute at Shenzhen
2018-2025
Chinese Academy of Agricultural Sciences
2009-2025
University of Tennessee Health Science Center
2016-2025
Sun Yat-sen University
2011-2024
Peking University
2002-2024
Third Affiliated Hospital of Sun Yat-sen University
2024
Guangxi University
2007-2023
Jinyintan Hospital
2020-2023
Guizhou University
2023
Sun Yat-sen University Cancer Center
2022
Toll-like receptors (TLRs) bind pathogen-specific ligands early in infection, initiating signaling pathways that lead to expression of multiple protective cellular genes. Many viruses have evolved strategies block the effector mechanisms induced through these pathways, but viral interference with critical proximal receptor interactions has not been described. We show here NS3/4A serine protease hepatitis C virus (HCV), a notorious for its ability establish persistent intrahepatic causes...
ABSTRACT Virus-responsive signaling pathways that induce alpha/beta interferon production and engage intracellular immune defenses influence the outcome of many viral infections. The processes trigger these their effect upon host permissiveness for specific pathogens are not well understood. We show structured hepatitis C virus (HCV) genomic RNA activates regulatory factor 3 (IRF3), thereby inducing in cultured cells. This response is absent cells selected HCV replication. Studies including...
Persistent infections with hepatitis C virus (HCV) are likely to depend on viral inhibition of host defenses. We show that the HCV NS3/4A serine protease blocks phosphorylation and effector action interferon regulatory factor-3 (IRF-3), a key cellular antiviral signaling molecule. Disruption function by mutation or ketoamide peptidomimetic inhibitor relieved this blockade restored IRF-3 after challenge an unrelated virus. Furthermore, dominant-negative constitutively active mutants,...
Hepatitis C virus (HCV) is a major human pathogen that infects 170 million people. A hallmark of HCV its ability to establish persistent infections reflecting the evasion host immunity and interference with alpha/beta-IFN innate immune defenses. We demonstrate disruption retinoic acid-inducible gene I (RIG-I) signaling by viral NS3/4A protease contributes control antiviral RIG-I was essential for or RNA-induced IFN-beta promoter in hepatoma cells. This disrupted activity NS3/4A, which...
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a novel that causes highly contagious disease, SARS, with significant mortality. Although factors contributing to the pathogenic nature of SARS-CoV remain poorly understood, it has been reported infection does not induce type I interferons (IFNs) in cell culture. However, uncertain whether evades host detection or evolved mechanisms counteract innate defenses. We show here triggers weak IFN response cultured human lung/bronchial...
Viral signaling through retinoic acid-inducible gene-I (RIG-I) and its adaptor protein, IFN promoter-stimulator 1 (IPS-1), activates regulatory factor-3 (IRF-3) the host IFN-alpha/beta response that limits virus infection. The hepatitis C (HCV) NS3/4A protease cleaves IPS-1 to block RIG-I signaling, but how this regulation controls HCV is not known. Moreover, endogenous cleavage has been demonstrated in context of infection vitro or vivo. Here, we show transiently induces RIG-I-...
ABSTRACT Dicistronic, selectable subgenomic replicons derived from the Con1 strain of hepatitis C virus (HCV) are capable autonomous replication in cultured Huh7 cells (Lohmann et al., Science 285:110-113, 1999). However, adaptive mutations NS3, NS5A, and/or NS5B proteins required for efficient these RNAs and increase by orders magnitude numbers G418-resistant colonies selected following transfection cells. Here, we demonstrate that a replicon (NNeo/3-5B) an infectious molecular clone second...
Innate cellular antiviral defenses are likely to influence the outcome of infections by many human viruses, including hepatitis B and C agents that frequently establish persistent infection leading chronic hepatitis, cirrhosis, liver cancer. However, little is known pathways which hepatocytes, cell type within these replicate, sense infection, initiate protective responses. We show cultured hepatoma cells, Huh7 do not activate interferon (IFN)-beta promoter in response extracellular...
Respiratory syncytial virus (RSV) is one of the most common viral pathogens causing severe lower respiratory tract infections in infants and young children. Infected host cells detect respond to RNA viruses using different mechanisms a cell-type-specific manner, including retinoic acid-inducible gene I (RIG-I)-dependent Toll-like receptor (TLR)-dependent pathways. Because relative contributions these two pathways recognition RSV infection are unknown, we examined their roles this study. We...
ABSTRACT Coronaviruses encode multifunctional proteins that are critical for viral replication and blocking the innate immune response to infection. One such domain is coronavirus papain-like protease (PLP), which processes replicase polyprotein, has deubiquitinating (DUB) activity, antagonizes induction of type I interferon (IFN). Here we characterized DUB IFN antagonism activities PLP domains human NL63 severe acute respiratory syndrome (SARS) determine if activity mediates antagonism. We...
Mitochondrial antiviral signaling protein (MAVS) is an essential component of virus-activated pathways that induce protective IFN responses. Its localization to the outer mitochondrial membrane suggests important yet unexplained role for mitochondria in innate immunity. Here, we show hepatitis A virus (HAV), a hepatotropic picornavirus, ablates type 1 responses by targeting 3ABC precursor its 3C(pro) cysteine protease where it colocalizes with and cleaves MAVS, thereby disrupting activation...
Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up host innate immune response. Here we show human coronavirus (HCoV) NL63 severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize mediated by STING (stimulator interferon genes, also known as MITA/ERIS/MYPS). resides in endoplasmic reticulum upon activation, forms dimers which assemble with MAVS, TBK-1 IKKε, leading IRF-3 activation...
Tripartite-motif protein-56 (TRIM56) positively regulates the induction of type I interferon (IFN) response via TLR3 pathway by enhancing IRF3 activation and depends on its C-terminal residues 621-750 for interacting with adaptor TRIF. However, precise underlying mechanism detailed TRIM56 determinants remain unclear. Herein, we show ectopic expression murine also enhances TLR3-dependent IFN-β promoter activation, suggesting functional conservation. We found that endogenous TRIF formed a...
The interferon-stimulated gene, viperin, has been shown to have antiviral activity against hepatitis C virus (HCV) in the context of HCV replicon, although molecular mechanisms responsible are not well understood. Here, we demonstrate that viperin plays an integral part ability interferon limit replication cell-culture-derived (JFH-1) accurately reflects complete viral life cycle. Using confocal microscopy and fluorescence resonance energy transfer (FRET) analysis, localizes interacts with...
Toll-like receptor-3 (TLR3) senses double-stranded RNA, initiating signaling that activates NF-kappaB and interferon regulatory factor 3 (IRF-3), thereby inducing the synthesis of proinflammatory cytokines, type I interferons, numerous interferon-stimulated genes (ISGs). This pathway has not been extensively investigated in human hepatocytes, its role sensing protecting against hepatitis virus infections is uncertain. We show here primary hepatocytes express TLR3 robustly upregulate ISGs...
Chemokines and inflammatory cytokines are key regulators of immunity inflammation during viral infections. Hepatitis C virus (HCV) is a hepatotropic RNA frequently associated with chronic liver hepatocellular carcinoma. Intrahepatic levels chemokines elevated in HCV infections, but the underlying mechanisms remain unclear. We found that Toll-like receptor-3 (TLR3) senses infection cultured hepatoma cells, leading to nuclear factor kappa B (NF-κB) activation production numerous cytokines,...
ABSTRACT The leader proteinase (L pro ) of foot-and-mouth disease virus (FMDV) is a papain-like that plays an important role in FMDV pathogenesis. Previously, it has been shown L involved the inhibition type I interferon (IFN) response by FMDV. However, underlying mechanisms remain unclear. Here we demonstrate Lb , shorter form deubiquitinating activity. Sequence alignment and structural bioinformatics analyses revealed catalytic residues (Cys51 His148) are highly conserved all seven...
Abstract Myostatin (MSTN) is a dominant inhibitor of skeletal muscle development and growth. Mutations in MSTN gene can lead to hypertrophy or double-muscled (DM) phenotype cattle, sheep, dog human. However, there has not been reported significant phenotypes pigs association with mutations. Pigs are an important source meat production, as well serve preferred animal model for the studies human disease. To study impacts mutations on growth pigs, we generated -mutant Meishan no marker via zinc...
Foot-and-mouth disease is a highly contagious viral illness of wild and domestic cloven-hoofed animals. The causative agent, foot-and-mouth virus (FMDV), replicates rapidly, efficiently disseminating within the infected host being passed on to susceptible animals via direct contact or aerosol route. To survive in host, FMDV has evolved block interferon (IFN) response. Previously, we others demonstrated that leader proteinase (L(pro)) an IFN antagonist. Here, report another FMDV-encoded...
Background:The pig is an economically important food source, amounting to approximately 40% of all meat consumed worldwide. Pigs also serve as model organism because their similarity humans at the anatomical, physiological and genetic level, making them very useful for studying a variety human diseases. A strain particular interest miniature pig, specifically Wuzhishan (WZSP), it has been extensively inbred. Its high level homozygosity offers increased ease selective breeding specific traits...
Toll-like receptor 3 (TLR3) and cytosolic RIG-I-like helicases (RIG-I MDA5) sense viral RNAs activate innate immune signaling pathways that induce expression of interferon (IFN) through specific adaptor proteins, TIR domain-containing inducing interferon-β (TRIF), mitochondrial antiviral protein (MAVS), respectively. Previously, we demonstrated hepatitis A virus (HAV), a unique hepatotropic human picornavirus, disrupts RIG-I/MDA5 by targeting MAVS for cleavage 3ABC, precursor the sole HAV...