A5101878366- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- Animal Virus Infections Studies
- RNA regulation and disease
- Viral gastroenteritis research and epidemiology
- Viral Infections and Vectors
- RNA Research and Splicing
- SARS-CoV-2 detection and testing
- Mosquito-borne diseases and control
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- COVID-19 Clinical Research Studies
- Epigenetics and DNA Methylation
- Biosensors and Analytical Detection
- Influenza Virus Research Studies
- Advanced biosensing and bioanalysis techniques
- Anesthesia and Sedative Agents
- Nuclear Structure and Function
- Invertebrate Immune Response Mechanisms
- Insect symbiosis and bacterial influences
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Anesthesia and Pain Management
- Respiratory viral infections research
- Cytokine Signaling Pathways and Interactions
Arizona State University
2021-2025
Washington University in St. Louis
2025
Hebei General Hospital
2024
University of Pennsylvania
2013-2023
Duke University Hospital
2023
Duke Medical Center
2023
Air Force Medical University
2023
Xijing Hospital
2023
State Key Laboratory of Food Science and Technology
2022
Jiangnan University
2022
Significance RNase L, an antiviral enzyme activated during infection, degrades viral and cellular RNAs, inhibits protein synthesis, restricts the replication spread of diverse viruses. L activation depends on 2′,5′-oligoadenylates synthesized by different oligoadenylate synthetases (OASs), i.e., OAS1, OAS2, OAS3. OASs are induced interferon dsRNA. It has been unclear which these OAS proteins is necessary and/or sufficient to activate infections. We show that OAS3, but not OAS1 or required...
Coronaviruses are of veterinary and medical importance include highly pathogenic zoonotic viruses, such as SARS-CoV MERS-CoV. They known to efficiently evade early innate immune responses, manifesting in almost negligible expression type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved prevent RNA-based sensing infection vertebrate hosts. Here we show the coronavirus endonuclease (EndoU) activity is key induction double-stranded...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases August 2020 (https://covid19.who.int/). There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments limited to supportive therapies off-label use drugs. Rapid development human testing potential is urgently needed. Numerous drugs already approved use, subsequently,...
Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase–ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which recently emerged SARS-CoV-2 activates antagonizes these is relatively unknown. We found that infects patient-derived nasal epithelial cells, present...
Abstract Antibody cocktails represent a promising approach to prevent SARS-CoV-2 escape. The determinants for selecting antibody combinations and the mechanism that viral escape remain unclear. We compared critical residues in receptor-binding domain (RBD) used by multiple neutralizing antibodies identified combination of two CoV2-06 CoV2-14 preventing simultaneously bind non-overlapping epitopes independently compete receptor binding. rapidly escapes from individual generating resistant...
ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of leads to a severe neurodevelopmental inflammatory disease children, Aicardi-Goutiéres syndrome. In mice, Adar1 mutations embryonic lethal but rescued by mutation the Mda5 or Mavs genes, which function in IFN induction. However, specific regulated proteins responsible for pathogenic effects unknown. We show cell-lethal phenotype deletion human lung...
Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human to emerge since severe acute (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins are not required for replication of genome but likely involved pathogenesis. Evasion host innate immunity through interferon (IFN) antagonism a critical component viral The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing...
Middle East respiratory syndrome coronavirus (MERS-CoV) is the second novel zoonotic to emerge in 21st century and cause outbreaks of severe disease. More than 2,200 cases 800 deaths have been reported date, yet there are no licensed vaccines or treatments. Coronaviruses encode unique accessory proteins that not required for replication but most likely play roles immune antagonism and/or pathogenesis. Our study describes functions MERS-CoV NS4a NS4b during infection a human airway-derived...
Abstract Background Rapid spread of SARS-CoV-2 has led to a global pandemic, resulting in the need for rapid assays allow diagnosis and prevention transmission. Reverse transcription-polymerase chain reaction (RT-PCR) provides gold standard assay RNA, but instrument costs are high supply chains potentially fragile, motivating interest additional methods. transcription loop-mediated isothermal amplification (RT-LAMP) an alternative that uses orthogonal often less expensive reagents without...
Short of a vaccine, frequent and rapid testing, preferably at home, is the most effective strategy to contain COVID-19 pandemic. Herein, we report on single-stage two-stage molecular diagnostic tests that can be carried out with simple or no instrumentation. Our amplification reverse transcription-loop mediated isothermal (RT-LAMP) custom-designed primers targeting ORF1ab N gene regions virus genome. new amplification, dubbed Penn-RAMP, comprises recombinase (RT-RPA) as its first stage LAMP...
Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA infections. However, DVGs can also facilitate persistence. Why and how these two opposing functions achieved remain unknown. Here we report that Sendai respiratory syncytial infections selectively protect a subpopulation cells from death, thereby promoting establishment persistent We find infection this phenotype results stimulating mitochondrial...
Significance Drugs that cause epigenetic modification of DNA, such as 5-azacytidine (AZA), are used clinically to treat myelodysplastic syndromes and acute myeloid leukemia. In addition, AZA is being investigated for use against a range different types solid tumors, including lung colorectal cancers. Treatment with causes demethylation thus increasing RNA synthesis, the synthesis double-stranded RNA, which otherwise produced in virus-infected cells. We determined cell death response requires...
The COVID-19 pandemic poses a serious global health threat. rapid spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking infection and spread. Stimulator Interferon Genes (STING) is chief element in host antiviral defense pathways. In this study, we examined the impact STING signaling pathway on coronavirus using human OC43 (HCoV-OC43) model. We found that HCoV-OC43 did not stimulate pathway, but activation effectively inhibits much greater extent than...
Coronaviruses (CoVs) are positive-sense RNA viruses that infect numerous mammalian and avian species capable of causing severe lethal disease in humans. CoVs encode several innate immune antagonists counteract the host response to facilitate efficient viral replication. CoV nonstructural protein 14 (nsp14) encodes 3'-to-5' exoribonuclease activity (ExoN), which performs a proofreading function is required for high-fidelity Outside order Nidovirales, arenaviruses only an ExoN, functions...
ABSTRACT Mouse hepatitis virus (MHV) isolates JHM.WU and JHM.SD promote severe central nervous system disease. However, while replicates robustly induces hepatitis, fails to replicate or induce pathology in the liver. These two JHM variants encode homologous proteins with few polymorphisms, little is known about which viral proteins(s) responsible for liver tropism of JHM.WU. We constructed reverse genetic systems and, utilizing these full-length cDNA clones, chimeric viruses mapped...
ABSTRACT The oligoadenylate synthetase (OAS)-RNase L pathway is a potent interferon (IFN)-induced antiviral activity. Upon sensing double-stranded RNA, OAS produces 2′,5′-oligoadenylates (2-5A), which activate RNase L. Murine coronavirus (mouse hepatitis virus [MHV]) nonstructural protein 2 (ns2) 2′,5′-phosphodiesterase (PDE) that cleaves 2-5A, thereby antagonizing activation. PDE activity required for robust replication in myeloid cells, as mutant of MHV (ns2 H126R ) encoding an inactive...
There is currently no knowledge of how the emerging human pathogen Zika virus (ZIKV) interacts with antiviral endoribonuclease L (RNase L) pathway during infection. Since activation RNase infection typically limits production dramatically, we used CRISPR-Cas9 gene editing technology to knockout (KO) targeted host genes involved in evaluate effects on ZIKV A549 cells. was activated response infection, which degraded genomic RNA. Surprisingly, despite viral genome reduction, activity did not...
Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which recently emerged SARS-CoV-2 activates antagonizes these is relatively unknown. We found that infects patient-derived nasal epithelial cells, present...
Previous studies have demonstrated that the murine coronavirus mouse hepatitis virus (MHV) nonstructural protein 2 (ns2) is a 2',5'-phosphodiesterase inhibits activation of interferon-induced oligoadenylate synthetase (OAS)-RNase L pathway. Enzymatically active ns2 required for efficient MHV replication in macrophages, as well induction C57BL/6 mice. In contrast, following intranasal or intracranial inoculation, brain not dependent on an enzymatically ns2. The wild-type strain A59 (A59) and...
Cells of all mammals recognize double-stranded RNA (dsRNA) as a foreign material. In response, they release interferons (IFNs) and activate ubiquitously expressed pseudokinase/endoribonuclease RNase L. L executes regulated decay halts global translation. Here, we developed biosensor for 2′,5′-oligoadenylate (2-5A), the natural activator Using this biosensor, found that 2-5A was acutely synthesized by cells in response to dsRNA sensing, which immediately triggered cellular cleavage arrested...
Coronavirus EndoU inhibits dsRNA-activated antiviral responses; however, the physiologic RNA substrates of are unknown. In this study, we used mouse hepatitis virus (MHV)-infected bone marrow-derived macrophage (BMM) and cyclic phosphate cDNA sequencing to identify targets EndoU. targeted viral RNA, cleaving 3' side pyrimidines with a strong preference for U
The severe acute respiratory coronavirus 2 (SARS-CoV-2) is the cause of global outbreak COVID-19. epidemic accelerated in Philadelphia, PA, spring 2020, with city experiencing a first peak infections on 15 April, followed by decline through midsummer. Here, we investigate spread wave Philadelphia using full-genome sequencing 52 SARS-CoV-2 samples obtained from 27 hospitalized patients collected between 30 March and 17 July 2020. Sequences most commonly resembled lineages circulating at...
// Shuvojit Banerjee 1 , Geqiang Li 1, * Yize 2 Christina Gaughan Danika Baskar Yvonne Parker 3 Daniel J. Lindner Susan R. Weiss Robert H. Silverman Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA Microbiology, Perelman School Medicine, University Pennsylvania, Philadelphia, Translational Hematology and Oncology Research,Taussig Current address: Abpro, 65 Cummings Park Drive, Woburn, MA Correspondence to: Silverman, e-mail: silverr@ccf.org...