A5028988991- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- interferon and immune responses
- COVID-19 Clinical Research Studies
- IL-33, ST2, and ILC Pathways
- Cytokine Signaling Pathways and Interactions
- Plant Virus Research Studies
- Advanced Thermodynamic Systems and Engines
- COVID-19 Impact on Reproduction
- RNA Research and Splicing
- Clostridium difficile and Clostridium perfringens research
- Escherichia coli research studies
- Mosquito-borne diseases and control
UConn Health
2021-2024
Yale University
2019-2021
Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with identified known factors including the receptor ACE2 protease Cathepsin L. We additionally discovered pro-viral pathways SWI/SNF chromatin remodeling complex key components TGF-β signaling pathway. Small molecule inhibitors these prevented SARS-CoV-2-induced cell death. also revealed that...
Murine norovirus (MNoV) is an important model of human (HNoV) and mucosal virus infection more broadly. Viral receptor utilization a major determinant cell tropism, host range, pathogenesis. The bona fide for HNoV unknown. Recently, we identified CD300lf as proteinaceous MNoV. Interestingly, its paralogue CD300ld was also sufficient MNoV in vitro. Here explored whether the sole physiologic vivo can use CD300 ortholog entry receptor. We report that both are by diverse strains further...
The persistent murine norovirus strain MNVCR6 is a model for human and enteric viral persistence. causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although induces functional MNV-specific CD8+ T these lymphocytes fail to clear infection. To examine how cells promote immune escape, we interrogated cell interactions with adoptively transferring JEDI (just EGFP death inducing) into Gfi1b-GFP reporter mice. Unexpectedly, some partially...
Murine norovirus (MNoV) is a model for human and interrogating mechanisms of viral tropism persistence. We previously demonstrated that the persistent strain MNoVCR6 infects tuft cells, which are dispensable non-persistent MNoVCW3. now show diverse MNoV strains require cells chronic enteric infection. also demonstrate interferon-λ (IFN-λ) acts directly on to cure infection type I III IFNs signal together via STAT1 in restrict MNoVCW3 tropism. then develop an enteroid find similarly infect...
Human noroviruses (HuNoVs) are a leading cause of gastroenteritis resulting in up to 200,000 deaths each year. The receptor and cell tropism HuNoV immunocompetent humans unclear.
Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit pathogenic evolutionary potential this enteric virus. In animals lacking type I signaling, nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion a single nucleotide. This nucleotide change resulted in amino acid substitution F514I capsid, which led...
Abstract Type I/III IFNs induce expression of hundreds IFN-stimulated genes through the JAK/STAT pathway to combat viral infections. Although signaling is seemingly straightforward, it nevertheless subjected complex cellular regulation. In this study, we show that an ubiquitination regulatory X (UBX) domain-containing protein, UBXN6, positively regulates JAK-STAT1/2 signaling. Overexpression UBXN6 enhanced type IFNs–induced genes, whereas deletion inhibited their expression. RNA replication...
Identification of host determinants coronavirus infection informs mechanisms pathogenesis and may provide novel therapeutic targets. Here, we demonstrate that the histone demethylase KDM6A promotes diverse coronaviruses, including SARS-CoV, SARS-CoV-2, MERS-CoV mouse hepatitis virus (MHV) in a activity-independent manner. Mechanistic studies reveal viral entry by regulating expression multiple receptors, ACE2 , DPP4 Ceacam1 . Importantly, TPR domain is required for recruitment...
Abstract Murine norovirus (MNoV) is an important model of human (HNoV) and mucosal virus infection more broadly. Viral receptor utilization a major determinant cell tropism, host range, pathogenesis. The bona fide for HNoV unknown. Recently, we identified CD300lf as proteinaceous MNoV. Interestingly, its paralogue CD300ld was also sufficient MNoV in vitro . Here explored whether the sole physiologic vivo can use CD300 ortholog entry receptor. We report that both are by diverse strains...
ABSTRACT Noroviruses are a leading cause of gastrointestinal infection in humans and mice. Understanding human norovirus (HuNoV) cell tropism has important implications for our understanding viral pathogenesis. Murine (MNoV) is extensively used as surrogate model HuNoV. We previously identified CD300lf the receptor MNoV. Here, we generated Cd300lf conditional knockout ( F/F ) mouse to elucidate persistent non-persistent strains murine norovirus. Using this model, demonstrate that expression...