A5042366783- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- Immune Response and Inflammation
- Influenza Virus Research Studies
- COVID-19 Clinical Research Studies
- HIV Research and Treatment
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Viral Infections and Immunology Research
- Inflammasome and immune disorders
- Viral Infections and Vectors
- RNA Research and Splicing
- Respiratory viral infections research
- Virus-based gene therapy research
- Virology and Viral Diseases
- Ubiquitin and proteasome pathways
- Phagocytosis and Immune Regulation
- RNA regulation and disease
- Click Chemistry and Applications
- Animal Virus Infections Studies
- RNA and protein synthesis mechanisms
- NF-κB Signaling Pathways
- Viral gastroenteritis research and epidemiology
The Ohio State University
2016-2025
The Ohio State University Wexner Medical Center
2020-2024
Columbus Oncology and Hematology Associates
2023
Infectious Diseases Institute
2022
Nationwide Children's Hospital
2022
Institute of Infection and Immunity
2020
Ohio University
2015-2018
Interface (United States)
2013-2017
Rockefeller University
2009-2017
Institut Pasteur
2016
Fatty-acylation of proteins in eukaryotes is associated with many fundamental cellular processes but has been challenging to study due limited tools for rapid and robust detection protein fatty-acylation cells. The development azido-fatty acids enabled the nonradioactive fatty-acylated mammalian cells using Staudinger ligation biotinylated phosphine reagents. However, visualization streptavidin blotting highly variable not ideal proteins. Here we report alkynyl-fatty acid chemical reporters...
Interferon-induced transmembrane proteins (IFITMs) restrict infections by many viruses, but a subset of IFITMs enhance specific coronaviruses through currently unknown mechanisms. We show that SARS-CoV-2 Spike-pseudotyped virus and genuine are generally restricted human mouse IFITM1, IFITM2, IFITM3, using gain- loss-of-function approaches. Mechanistically, restriction occurred independently IFITM3 S-palmitoylation, indicating restrictive capacity distinct from reported inhibition other...
The interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that inhibits infection by influenza virus and many other pathogenic viruses. IFITM3 prevents endocytosed particles from accessing the host cytoplasm although little known regarding its regulatory mechanisms. Here we demonstrate localization to antiviral remodeling of endolysosomes differentially regulated S-palmitoylation lysine ubiquitination. Although enhances membrane affinity activity,...
Significance Cysteine fatty acylation (S-fatty acylation) regulates the stability, trafficking, and activity of proteins in eukaryotes. Current methods to study S-fatty rely on metabolic incorporation acid analogs or selective chemical labeling affinity purification, which limits detection endogenous acylated protein isoforms levels. Here we demonstrate that biochemical exchange acyl groups cysteines with defined mass-tags enables direct visualization The application this mass-tag method...
Interferon-inducible transmembrane protein 3 (IFITM3) is essential for innate defense against influenza virus in mice and humans. IFITM3 localizes to endolysosomes where it prevents fusion, although mechanisms controlling its trafficking this cellular compartment are not fully understood. We determined that both mouse human phosphorylated by the protein-tyrosine kinase FYN on tyrosine 20 (Tyr20) also non-conserved Tyr27. Phosphorylation led a redistribution of IFITM3, including plasma...
Traditional Chinese Medicines (TCMs) have been historically used to treat bacterial infections. However, the molecules responsible for these anti-infective properties and their potential mechanisms of action remained elusive. Using a high-throughput assay type III protein secretion in Salmonella enterica serovar Typhimurium, we discovered that several TCMs can attenuate this key virulence pathway without affecting growth. Among active TCMs, baicalein, specific flavonoid from Scutellaria...
Interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cell-intrinsic factor that limits influenza virus infections. We previously showed IFITM3 degradation increased by its ubiquitination, though the ubiquitin ligase responsible for this modification remained elusive. Here, we demonstrate E3 NEDD4 ubiquitinates in cells and vitro. This ubiquitination dependent upon presence of PPxY motif within WW domain-containing region NEDD4. In knockout mouse embryonic fibroblasts, observed...
Sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) blocks replication of retroviruses certain DNA viruses by reducing the intracellular dNTP pool. SAMHD1 has been suggested to down-regulate IFN inflammatory responses viral infections, although functions mechanisms in modulating innate immunity remain unclear. Here, we show that suppresses immune infections stimuli inhibiting nuclear factor-κB (NF-κB) activation type I interferon (IFN-I) induction. Compared with control cells,...
Rapid and specific antibody testing is crucial for improved understanding, control, treatment of COVID-19 pathogenesis. Herein, we describe apply a rapid, sensitive, accurate virus neutralization assay SARS-CoV-2 antibodies. The based on an HIV-1 lentiviral vector that contains secreted intron Gaussia luciferase (Gluc) or nano-luciferase reporter cassette, pseudotyped with the spike (S) glycoprotein, validated plaque-reduction using authentic, infectious strain. was used to evaluate...
ABSTRACT Human and mouse SAMHD1 proteins block human immunodeficiency virus type 1 (HIV-1) infection in noncycling monocytic cells by reducing the intracellular deoxynucleoside triphosphate (dNTP) concentrations. Phosphorylation of at threonine 592 (T592) cyclin-dependent kinase (CDK1) cyclin A2 impairs its HIV-1 restriction activity, but not dNTP hydrolase suggesting that depletion is sole mechanism SAMHD1-mediated restriction. Using coimmunoprecipitation mass spectrometry, we identified...
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is a novel and highly pathogenic the causative agent of disease 2019 (COVID-19). The high morbidity mortality associated with COVID-19 lack an approved drug or vaccine for SARS-CoV-2 underscores urgent need developing effective antiviral therapies. Therapeutics that target essential viral proteins are at controlling virus replication spread. Coronavirus Spike glycoproteins mediate entry fusion host cell, thus replication. To enter...
Significance We discovered that IFITM3 prevents efficient dissemination and replication of influenza virus in heart tissue, thereby limiting cardiac fibrosis electrical dysfunction during infection. Since polymorphisms are among the only human genetic factors have been reproducibly associated with hospitalization mortality infection, our findings relevant to serious threat infection health. Furthermore, KO mice provide one first models for studying complications influenza.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which rare cases long term debilitating arthritis and arthralgia. Significant progress has been made understanding the roles of canonical RNA sensing pathways host recognition CHIKV; however, less regarding antagonism CHIKV by cytosolic DNA like that cyclic GMP-AMP synthase (cGAS) Stimulator Interferon Genes (STING). With use cGAS or STING null cells we...
Significance Measles virus (MeV) vaccine is one of the safest and most efficient vaccines with a track record in children. Here, we generated panel rMeV-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S antigens inserted near 3′ MeV genome. The rMeV expressing soluble stabilized, prefusion spike (preS) much more potent triggering SARS-CoV-2–specific neutralizing antibody than full-length candidate. A single dose rMeV-preS sufficient to induce high levels SARS-CoV-2...
Significance We report the discovery of fundamental roles for noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role immune responses beyond its previously appreciated effects bacterial Further, we show Caspase-11–deficient mice infected with SARS–CoV-2 fare significantly better terms overall illness, lung...
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main target for neutralizing antibodies (NAbs). S trimer anchored in virion membrane its prefusion (preS) but metastable form. preS has been stabilized by introducing two or six proline substitutions, to generate stabilized, soluble 2P HexaPro (6P) proteins. Currently, it not known which form most immunogenic. Here, we generated recombinant vesicular stomatitis virus (rVSV) expressing preS-2P,...
Abstract Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral that alters cell membranes to block fusion of viruses. Conflicting reports identified opposing effects IFITM3 on SARS‐CoV‐2 infection cells, and its impact viral pathogenesis in vivo remains unclear. Here, we show knockout (KO) mice infected with experience extreme weight loss lethality compared mild wild‐type (WT) mice. KO have higher lung titers increases inflammatory cytokine levels, immune infiltration,...
Abstract Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation GSDMD in knockout (KO) mice ( Gsdmd −/− ) significantly attenuates influenza virus-induced weight loss, lung dysfunction, histopathology, mortality compared with wild type (WT) mice, despite similar viral loads. Infected exhibit...