A5011838203- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Respiratory viral infections research
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Bacteriophages and microbial interactions
- Immune Response and Inflammation
- RNA Research and Splicing
- SARS-CoV-2 and COVID-19 Research
- Diabetes and associated disorders
- RNA modifications and cancer
- Antifungal resistance and susceptibility
- interferon and immune responses
- Bacterial Genetics and Biotechnology
- Plant Virus Research Studies
- Animal Disease Management and Epidemiology
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Fungal Infections and Studies
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Plant Disease Resistance and Genetics
- PARP inhibition in cancer therapy
Center for Biologics Evaluation and Research
2011-2023
United States Food and Drug Administration
2011-2022
Medical University of South Carolina
2012
University of Maryland, College Park
2002-2007
Office of Extramural Research
2007
University of Massachusetts Chan Medical School
2002
University of Otago
1998-2000
A wide range of RNA viruses use programmed -1 ribosomal frameshifting for the production viral fusion proteins. Inspection overlap regions between ORF1a and ORF1b SARS-CoV genome revealed that, similar to all coronaviruses, a frameshift could be used by virus produce protein. Computational analyses signal predicted presence an mRNA pseudoknot containing three double-stranded stem structures rather than two. Phylogenetic showed conservation potential three-stemmed pseudoknots in signals other...
The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and NH vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 isolates. All three populations (children, adults, older adults) vaccinated the egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination...
ABSTRACT In retroviruses and the double-stranded RNA totiviruses, efficiency of programmed −1 ribosomal frameshifting is critical for ensuring proper ratios upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations many other viruses, including coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, frameshift-dependent downstream enzymes involved transcription replication, structural encoded by...
In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations programmed ribosomal frameshift signal ORF1a/b were observed. It was not clear if these due to changes sequence, protein sequence or frequency frameshifting. Here, viruses synonymous codon are shown produce different ratios RNA. These findings demonstrate that is primary cause altered production. The affect both structure frameshifting efficiency. Small efficiency result...
mRNA pseudoknots have a stimulatory function in programmed −1 ribosomal frameshifting (−1 PRF). Though we previously presented model for how might activate the mechanism PRF, it did not address question of role that they may play positioning relative to ribosome this process [E. P. Plant, K. L. M. Jacobs, J. W. Harger, A. Meskauskas, Baxter, N. Petrov and D. Dinman (2003) RNA , 9, 168–174]. A separate 'torsional restraint' suggests act increase fraction ribosomes directed pause with upstream...
Abstract Messenger RNA encoded signals that are involved in programmed -1 ribosomal frameshifting (-1 PRF) typically two-stemmed hairpin (H)-type pseudoknots (pks). We previously described an unusual three-stemmed pseudoknot from the severe acute respiratory syndrome (SARS) coronavirus (CoV) stimulated PRF. The conserved existence of a third stem–loop suggested important hitherto unknown function. Here we present new information describing structure and function stem SARS pseudoknot....
ABSTRACT Antibodies against the neuraminidase (NA) of influenza virus correlate with resistance disease, but effectiveness antibodies different NA epitopes has not been compared. In present study, we evaluated in vitro and vivo efficacies four monoclonal (MAbs): HF5 CD6, which are specific to two 2009 pandemic H1N1 (pH1N1) virus, 4E9 1H5, a conserved epitope both H5N1 viruses. assays, CD6 inhibited spread growth more effectively than being most effective inhibitor. When administered...
The cis-acting mRNA elements that promote programmed -1 ribosomal frameshifting present a natural target for the rational design of antiretroviral chemotherapies. It has been commonly accepted HIV-1 signal is special, because its downstream enhancer element consists simple stem loop rather than more complex secondary structure such as pseudoknot. Here we three lines evidence, bioinformatic, structural, and genetic, showing biologically relevant frameshift contains RNA likely includes an...
Development of vaccines to prevent severe acute respiratory syndrome (SARS) is limited by the lack well-characterized animal models. Previous vaccine reports have noted robust neutralizing antibody and inflammatory responses in ferrets, resulting enhanced hepatitis.We evaluated humoral immune response pathological end points ferrets challenged with Urbani strain SARS-associated coronavirus (SARS-CoV) after having received formalin-inactivated whole-virus or mock vaccine.Humoral were observed...
Abstract Post-vaccination cytokine levels from 256 young adults who subsequently suffered breakthrough influenza infections were compared with matched controls. Modulation within the immune system is important for eliciting a protective response, and optimal response differs according to vaccine formulation delivery. For both inactivated (IIV) live attenuated vaccines (LAIV) lower of IL-8 observed in post-vaccination sera. antibody higher IFN-γ IIV sera LAIV Subjects after vaccination had...
Studies of programmed −1 ribosomal frameshifting (−1 PRF) have been approached over the past two decades by many different laboratories using a diverse array virus-derived frameshift signals in translational assay systems derived from variety sources. Though it is generally acknowledged that both absolute and relative PRF efficiency can vary an system-dependent manner, no methodical study this phenomenon has undertaken. To address issue, series slippery site mutants SARS-associated...
Decoding of mRNAs is performed by aminoacyl tRNAs (aa-tRNAs). This process highly accurate, however, at low frequencies (10(-3) - 10(-4)) the wrong aa-tRNA can be selected, leading to incorporation aberrant amino acids. Although our understanding what constitutes correct or cognate aa-tRNA:mRNA interaction well defined, a functional distinction between near-cognate single mismatched, and unpaired non-cognate interactions lacking.Misreading several synonymous codon substitutions catalytic...
The campaign of 2009–2010 Northern Hemisphere seasonal vaccination was concurrent with the 2009 H1N1 pandemic. Using a hemagglutination inhibition (HAI) assay, we evaluated immunogenicity and cross-reactivity inactivated trivalent influenza vaccine (TIV) in US adult elderly populations. Vaccination TIV resulted robust boost on antibody response all subjects to A/Brisbane/59/2007 (H1N1) A/Uruguay/716/2007 (H3N2) over 70% recipients reaching seroprotective titer 40. B/Brisbane/60/2008 least...
Nonsense‐mediated mRNA decay (NMD) directs rapid degradation of premature termination codon (PTC)‐containing mRNAs, e.g. those containing frameshift mutations. Many viral mRNAs encode polycistronic messages where programmed –1 ribosomal (–1 PRF) signals direct ribosomes to synthesize polyproteins. A previous study, which identified consensus PRF in the yeast genome, found that, contrast viruses, majority predicted events would translating PTCs. Here we tested hypothesis that a signal can...
The 2009 H1N1 pandemic viruses are genetically similar to A/New Jersey/76 virus (NJ/76), the strain selected for 1976 "swine flu" vaccines. Approximately 45 million people in United States were vaccinated against NJ/76 30 years ago, but impact of this nationwide immunization on current is largely unknown.Archived human serum samples collected during swine flu vaccine trials assessed cross-reactive antibody responses viruses.Administration an monovalent or combination a bivalent (NJ/76 and...
Effectiveness of seasonal influenza vaccines mainly depends upon how well vaccine strains represent circulating viruses; mismatched can lead to reduced protection. Humans have complex exposure histories that increase with age, which may different postvaccination responses emerging variants. Recent observational studies also suggest prior vaccination influence the performance current vaccines.To elucidate effects age and preexposures on cross-reactivity vaccination-induced human antibodies,...
Seasonal influenza vaccine formulas change almost every year yet information about how this affects the antibody repertoire of recipients is inadequate. New virus strains are selected, replacing older to better match currently circulating strains. But even while being manufactured can evolve. The ideal response a seasonal would maintain antibodies toward existing that might continue circulate, and generate cross-reactive antibodies, particularly towards conserved epitopes, potentially...
Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and closely related Kappa variant cause viral pneumonia severe lung lesions mice. Human COVID-19 mRNA post-vaccination sera after 2nd dose are significantly less efficient neutralizing Delta/Kappa than early 614G virus vitro vivo. By 5 months post-vaccination, ≥50% of donors lack detectable antibodies against all mice receiving 5-month die lethal...
Clinical samples from people with influenza disease have been analyzed to assess the presence and abundance of Defective Viral Genomes (DVGs), but these not assessed using same bioinformatic pipeline. The type DVG most described for infections (deletion DVGs) differs commonly DVGs non-segmented negative stranded viruses (5′ copyback). This could be attributed either differences between or tools used detect characterize DVGs. Here we analyze several NGS datasets infected different types virus...
HCV (hepatitis C virus) research, including therapeutics and vaccine development, has been hampered by the lack of suitable tissue culture models. Development cell systems for growth most drug-resistant genotype (1b) as well natural isolates remained a challenge. Transfection cultured cells with adenovirus-associated RNAI (VA RNAI), known interferon (IFN) antagonist inhibitor dsRNA-mediated antiviral pathways, enhanced plasma-derived 1b. Furthermore, persistent viral was achieved after...