A5032751745- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- RNA regulation and disease
- Virus-based gene therapy research
- RNA Research and Splicing
- interferon and immune responses
- Genomics and Chromatin Dynamics
- Viral Infections and Immunology Research
- Plant Virus Research Studies
- Viral Infections and Outbreaks Research
- Bat Biology and Ecology Studies
- Protein Degradation and Inhibitors
- Virology and Viral Diseases
- Tryptophan and brain disorders
- Viral Infections and Vectors
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Respiratory viral infections research
- Neuroinflammation and Neurodegeneration Mechanisms
- Histone Deacetylase Inhibitors Research
- Rabies epidemiology and control
- Gut microbiota and health
EpiCypher (United States)
2023-2024
The University of Texas Medical Branch at Galveston
2017-2021
Texas Medical Center
2021
University of North Carolina at Chapel Hill
2017-2019
Public Health Department
2017
Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs ability infect humans without adaptation. These results suggested additional barriers limit zoonotic CoV. In this work, we describe overcoming host restriction two Middle East (MERS)-like bat using exogenous protease treatment. We found spike protein PDF2180-CoV,...
Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' are read by specialized regions (reader domains) chromatin-associated proteins (CAPs) to regulate downstream function. Substantial effort made define [CAP: histone PTM] specificities, and thus decipher the code guide epigenetic therapies. However, this largely done using reductive approach of isolated reader domains peptides, which cannot...
ABSTRACT While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) ORFs (deletion ORF3, -4a, -4b, -5 [dORF3-5]) has major implications replication Importantly, attenuation dORF3-5 mutant is primarily driven by dysregulated host responses, including...
Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well genetic elements necessary for infection pathogenesis, raising the possibility common targets attenuation therapeutic design. In this study, we focused on nonstructural protein 16 (NSP16), viral 2'O-methyltransferase (2'O-MTase) that encodes critical functions in immune modulation infection. Using reverse genetics, disrupted key motif KDKE Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) evaluated...
Many host RNA sensors are positioned in the cytosol to detect viral during infection. However, most positive-strand viruses replicate within a modified organelle co-opted from intracellular membranes of endomembrane system, which shields products cellular innate immune sensors. Targeting system may enhance their ability sense generated by that use these compartments for replication. Here, we reveal an isoform oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted system. Membrane...
Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed stem future outbreaks. However, failure of many previous CoV formulations has clearly highlighted the need test efficacy under different conditions especially in vulnerable populations such as aged immunocompromised. This study illustrates that despite success young models, 2′O methyltransferase mutant carries too much risk for pathogenesis reversion models be used...
Based on genome-scale loss-of-function screens we discovered that Topoisomerase III-β (TOP3B), a human topoisomerase acts DNA and RNA, is required for yellow fever virus dengue virus-2 replication. Remarkably, found TOP3B efficient replication of all positive-sense-single stranded RNA viruses tested, including SARS-CoV-2. While there are no drugs specifically inhibit this topoisomerase, posit an attractive anti-viral target.
Abstract Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding new host. Our previous work with SARS-like viruses argued that bats already harbor CoVs ability infect humans without adaptation. These results suggested additional barriers limit zoonotic CoV. In this work, we describe overcoming host restriction two MERS-like bat using exogenous protease treatment. We found spike protein PDF2180-CoV, virus Ugandan bat, could mediate infection...
Abstract With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved proteins as a strategy generate live-attenuated vaccine strains against current and future CoVs. this in mind, we explored whether manipulation of CoV NSP16, 2’O methyltransferase (MTase), could provide broad attenuation platform strains. Using SARS-CoV mouse model, NSP16 mutant was evaluated...
Abstract Based on genome-scale loss-of-function screens we discovered that Topoisomerase III-ß (TOP3B), a human topoisomerase acts DNA and RNA, is required for yellow fever virus dengue virus-2 replication. Remarkably, found TOP3B efficient replication of all positive-sense-single stranded RNA viruses tested, including SARS-CoV-2. While there are no drugs specifically inhibit this topoisomerase, posit an attractive anti-viral target.
SUMMARY Many host RNA sensors are positioned in the cytosol to detect viral during infection. However, most positive-strand viruses replicate within a modified organelle co-opted from intracellular membranes of endomembrane system, which shields products cell innate immune sensors. Targeting system may enhance their ability sense generated by that use these compartments for replication. Here, we reveal an isoform oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted system....
Abstract Coronaviruses encode a mix of highly conserved and novel genes as well genetic elements necessary for infection pathogenesis, raising the possibility common targets attenuation therapeutic design. In this study, we focus on nonstructural protein (NSP) 16, viral 2’O methyl-transferase (MTase) that encodes critical functions in immune modulation infection. Using reverse genetics, disrupted key motif KDKE MERS NSP16 (D130A) evaluated effect pathogenesis. While absence MTase activity...
Abstract While improved sanitation and medical care have reduced the burden of infectious disease, it remains 4th leading cause death in elderly. Coupled with expansion aged population over next two decades, understanding interplay between infection senescent host is critical. Both microbiome genetics been predicted to play critical roles aging immunity. In this work, we explore role each age-dependent susceptibility virus infection. Severe acute respiratory syndrome coronavirus (SARS-CoV),...