A5039935202- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Influenza Virus Research Studies
- Respiratory viral infections research
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Microbial Metabolism and Applications
- Viral Infections and Immunology Research
- Immune Cell Function and Interaction
- Plant Virus Research Studies
- Animal Virus Infections Studies
Duke University
2020-2024
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or experience breakthrough infections. Understanding common host factors necessary for life cycles of may reveal conserved therapeutic targets. Here, we used known substrate specificities mammalian protein kinases to deconvolute...
ABSTRACT While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies treat patients who become infected. Pharmacological targeting of a host factor required viral replication can suppress spread with low probability mutation leading resistance. In particular, kinases highly druggable targets and number conserved coronavirus proteins, notably the nucleoprotein (N), require phosphorylation full functionality. order understand how could be used...
Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that virus must co-opt complete its replication cycle. However, detailed understanding interactions between and cell necessary order facilitate development host-directed therapeutics. As first step, we performed genome-wide loss function screen using alphacoronavirus HCoV-229E better...
Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of hemagglutinin (HA) glycoprotein. Because viral antigenic drift at these sites, need to be updated and readministered annually. To increase breadth vaccine-mediated protection, we developed an antigenically complex mixture recombinant HAs designed redirect immune more conserved domains protein. Vaccine-induced antibodies were disproportionally...
The CRISPR-Cas13 system has been proposed as an alternative treatment of viral infections. However, for this approach to be adopted antiviral, it must optimized until levels efficacy rival or exceed the performance conventional approaches. To take steps toward goal, we evaluated influenza RNA degradation patterns resulting from binding and enzymatic activity mRNA-encoded LbuCas13a two crRNAs a prior study, targeting PB2 genomic messenger RNA. We found that genome guide potential...
ABSTRACT Seasonal influenza vaccines provide mostly strain-specific protection due to the elicitation of antibody responses focused on evolutionarily plastic antigenic sites in hemagglutinin head domain. To direct humoral response toward more conserved epitopes, we generated an virus particle where full-length protein was replaced with a membrane-anchored, “headless” variant while retaining normal complement other viral structural proteins such as neuraminidase well RNAs. We found that...
Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth durability, it is desirable deliver both viral hemagglutinin neuraminidase glycoproteins. Delivering multiple antigens individually, however, complicates manufacturing increases cost, thus would be beneficial express proteins from a single mRNA. Here, we develop an mRNA genetic...
Influenza A viruses encode their genomes across eight, negative sense RNA segments. The six largest segments produce mRNA transcripts that do not generally splice; however, the two smallest are actively spliced to essential viral proteins NEP and M2. Thus, utilization of splicing effectively expands coding capacity without increasing number genomic As a first step towards understanding why is more broadly utilized segments, we designed inserted an artificial intron into normally nonsplicing...