A5038224842- interferon and immune responses
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Influenza Virus Research Studies
- Animal Virus Infections Studies
- Inflammasome and immune disorders
- Immune Cell Function and Interaction
- Viral Infections and Vectors
- Cytokine Signaling Pathways and Interactions
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- Cell death mechanisms and regulation
- Tryptophan and brain disorders
- IL-33, ST2, and ILC Pathways
- Protein Tyrosine Phosphatases
- RNA Research and Splicing
- Viral-associated cancers and disorders
- Microtubule and mitosis dynamics
- Receptor Mechanisms and Signaling
- Hepatitis C virus research
- Viral Infectious Diseases and Gene Expression in Insects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA Interference and Gene Delivery
- RNA regulation and disease
Ionis Pharmaceuticals (United States)
2021
McGill University
2006-2014
Jewish General Hospital
2006-2014
Vaccine & Gene Therapy Institute of Florida
2011
Terry Fox Research Institute
2006-2010
Bipar
2006-2009
Molecular Oncology (United States)
2006
ABSTRACT Intracellular RNA virus infection is detected by the cytoplasmic helicase RIG-I that plays an essential role in signaling to host antiviral response. Recently, adapter molecule links sensing of incoming viral downstream and gene activation events was characterized four different groups; MAVS/IPS-1-1/VISA/Cardif contains amino-terminal CARD domain a carboxyl-terminal mitochondrial transmembrane sequence localizes membrane. Furthermore, hepatitis C NS3-4A protease complex specifically...
The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic and viral structures that contain short hairpin dsRNA 5′ triphosphate (5′ppp) terminal structure. In the present study, an agonist of was synthesized in vitro shown to stimulate RIG-I-dependent antiviral responses at concentrations picomolar range. human lung epithelial A549 cells, 5′pppRNA specifically multiple parameters innate response, including IRF3, IRF7 STAT1 activation, induction...
The mitochondria-bound adapter MAVS participates in IFN induction by recruitment of downstream partners such as members the TRAF family, leading to activation NF-kappaB, and IRF3 pathways. A yeast two-hybrid search for MAVS-interacting proteins yielded Polo-box domain (PBD) mitotic Polo-like kinase PLK1. We showed that PBD associates with two different domains both dependent independent phosphorylation events. phosphodependent association requires phosphopeptide binding ability PBD. It takes...
Induction of the antiviral interferon response is initiated upon recognition viral RNA structures by RIG-I or Mda-5 DEX(D/H) helicases. A complex signaling cascade then converges at mitochondrial adapter MAVS, culminating in activation IRF and NF-kappaB transcription factors induction gene expression. We have previously shown that MAVS recruits IkappaB kinase epsilon (IKKepsilon) but not TBK-1 to mitochondria following infection. Here we map interaction IKKepsilon C-terminal region...
X-linked inhibitor of apoptosis (XIAP) is a potent antagonist caspase 3-, 7-, and 9-dependent apoptotic activities that functions as an E3 ubiquitin ligase, it targets caspases for degradation. In this study, we demonstrate Sendai virus (SeV) infection results in the IKKε- or TBK1-mediated phosphorylation XIAP vivo at Ser430, resulting Lys(48)-linked autoubiquitination Lys322/328 residues, followed by subsequent proteasomal degradation XIAP. Interestingly, IKKε expression turnover increases...
The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic and viral structures that contain short hairpin dsRNA 59 triphosphate (59ppp) terminal structure.In the present study, an agonist of was synthesized in vitro shown to stimulate RIG-I-dependent antiviral responses at concentrations picomolar range.In human lung epithelial A549 cells, 59pppRNA specifically multiple parameters innate response, including IRF3, IRF7 STAT1 activation,...
Abstract Primary effusion lymphoma (PEL) is a herpesvirus-8-associated lymphoproliferative disease characterized by migration of tumor cells to serous body cavities. PEL originate from postgerminal center B and share remarkable alteration in cell transcription factor expression and/or activation with classical Hodgkin’s cells. Comparative analysis gene cDNA microarray BCBL-1 (PEL), L-428 (classical disease), BJAB revealed subset genes that were differentially expressed Among these, four...
ABSTRACT Nucleic acid-based PS-ASOs have the potential to activate cellular innate immune responses, and level of activation can vary quite dramatically with sequence. Minimizing degree proinflammatory effect is one main selection criteria for compounds intended move into clinical trials. While a recently developed hPBMC-based assay showed excellent ability detect active PS-ASOs, which then be discarded from developmental process, this highly resource-intensive easily affected by subject...
Cytosolic sensing of incoming RNA virus infection is recognized by the DExD/H box helicases RIG‐I and Mda5. The mitochondrial adaptor MAVS links viral RIG‐I/Mda5 to downstream signaling, resulting in induction pro‐inflammatory antiviral genes NF‐ κB IRF respectively. We have demonstrated that NEMO, IKK complex, induces activation IRF3/7, acting but upstream TBK1/IKKε. NEMO requires TANK mediate recruitment kinases phosphorylation IRF3/7. Thus, bridges NF‐κB components with formation a...