A5046479135- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Malaria Research and Control
- Viral Infections and Outbreaks Research
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- HIV Research and Treatment
- Respiratory viral infections research
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Neonatal Respiratory Health Research
- Signaling Pathways in Disease
- Virology and Viral Diseases
- Cell Adhesion Molecules Research
- Animal Virus Infections Studies
- Enzyme Structure and Function
- Biochemical and Molecular Research
- Insect symbiosis and bacterial influences
- Viral Infectious Diseases and Gene Expression in Insects
- Enzyme function and inhibition
- Cardiac Fibrosis and Remodeling
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2024
United States Military Academy
2023
The University of Texas Medical Branch at Galveston
2004-2015
John Sealy Hospital
2009-2012
University of Rochester
2009
University of Liverpool
2009
Centers for Disease Control and Prevention
2005-2006
United States Department of Health and Human Services
2005-2006
The introduction of West Nile virus (WNV) into North America has been associated with relatively high rates neurological disease and death in humans, birds, horses, some other animals. Previous studies identified strains both genetic lineage 1 2, including American isolates 1, that were highly virulent a mouse neuroinvasion model, while avirulent or significantly attenuated (D. W. C. Beasley, L. Li, M. T. Suderman, A. D. Barrett, Virology 296:17-23, 2002). To begin to elucidate the basis for...
The NY99 genotype of West Nile virus (WNV) introduced into North America has demonstrated high virulence for American crows (AMCRs), whilst a closely related WNV strain (KEN-3829) from Kenya exhibits substantially reduced in AMCRs [Brault, A. C., Langevin, S. A., Bowen, R. Panella, N. Biggerstaff, B. J., Miller, & Nicholas, K. (2004). Emerg Infect Dis 10, 2161-2168]. Viruses rescued infectious cDNA clones both the and KEN-3829 strains comparable to that their parental AMCRs. To begin define...
The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus Disease 2019 (COVID-19) has spread through globe at an alarming speed. disease become a global pandemic affecting millions people and created public health crises worldwide. Among many efforts to urgently develop vaccine against this disease, we developed industrial-scale closed, single use manufacturing process for V590, candidate SARS-CoV-2. V590 is recombinant vesicular...
OBJECTIVE: Glioblastoma multiforme is the most frequent primary brain tumor in adults. The major obstacle for successful treatment invasive growth pattern. Metabolically, glioblastomas are highly glycolytic, leading to increased levels of lactic acid production. carbonic anhydrase IX (CAIX) moderates extrusion hydrogen ions into extracellular space, which may enhance invasion by activating proteolytic enzymes. We therefore induced glycolysis glioblastoma cells and investigated pH, cathepsin...
Vaccine immunogenicity and clinical efficacy are often assessed by the measure of serum-neutralizing antibodies. The present gold standard for detecting neutralizing antibodies against many viruses, including dengue, is plaque/focus reduction neutralization test (P/FRNT). FRNT a cell-based assay that inherits high variability, resulting in poor precision has lengthy turnaround times. virus (VRNT) high-throughput alternative to low-throughput laborious FRNT. VRNT similar using unaltered...
Chimeric dengue serotype 2/West Nile (D2/WN) viruses expressing prM-E of WN NY99 virus in the genetic background wild-type D2 16681 and two candidate PDK-53 vaccine variants (PDK53-E PDK53-V) were engineered. The viability D2/WN required incorporation virus-specific signal sequence for prM. Introduction mutations at M-58 E-191 chimeric cDNA clones further improved chimeras constructed all three carriers. Two (D2/WN-E2 -V2) engineered backbone PDK53-E -V retained characteristic phenotypic...
TEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern in astrocytic and metastatic brain tumors investigated its role as a therapeutic target human endothelial cells mouse xenograft models.In situ hybridization (ISH), immunohistochemistry (IH) immunofluorescence (IF) were used to localize grade II-IV astrocytomas on tissue microarrays. Changes response pro-angiogenic conditions assessed grown vitro. Intracranial U87MG glioblastoma...
The elderly are known to have enhanced susceptibility infections and an impaired capacity respond vaccination. West Nile virus (WNV), a mosquito-borne flavivirus, has induced severe neurological symptoms, mostly in the population. No vaccines available for human use. Recent work showed that attenuated WNV, nonstructural (NS) 4B-P38G mutant, no lethality but strong immune responses young (6- 10-week-old) mice. While studying protective efficacy, we found unexpectedly old (21- 22-month) mice...
We previously reported mutations in North American West Nile viruses (WNVs) with a small-plaque (sp), temperature-sensitive (ts), and/or mouse-attenuated (att) phenotype. Using an infectious clone, site-directed and 3' untranslated region (3'UTR) exchanges were introduced into the WNV NY99 genome. Characterization of mutants demonstrated that combination involving NS4B protein (E249G) together either mutation NS5 (A804V) or three 3'UTR (A10596G, C10774U, A10799G) produced sp, ts, att...
ABSTRACT We have previously shown that ablation of the three N-linked glycosylation sites in West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). Here, we compared replication 130-132QQA/175A/207A mutant to parental NY99 strain monkey kidney Vero cells. The results suggest mechanism attenuation is a lack glycosylation, which blocks efficient replication, maturation, and secretion from endoplasmic reticulum changes virus-induced ultrastructure.
Previous mutational analyses of naturally occurring West Nile virus (WNV) strains and engineered mutant WNV have identified locations in the viral genome that can profound phenotypic effect on infectivity, temperature sensitivity neuroinvasiveness. We chose six to evaluate for vector competence natural Culex tarsalis, two which contain multiple ablations glycosylation sites envelope NS1 proteins; three mutations NS4B protein an attenuated bird isolate (Bird 1153) harbouring mutation. Despite...
The rapid development of potency assays is critical in the life-saving vaccines. traditional plaque assay or fifty percent tissue culture infectious dose (TCID
An attenuated West Nile virus (WNV), a nonstructural (NS) 4B-P38G mutant, induced higher innate cytokine and T cell responses than the wild-type WNV in mice. Recently, myeloid differentiation factor 88 (MyD88) signaling was shown to be important for initial priming memory development during NS4B-P38G mutant infection. In this study, two flow cytometry-based methods – an vitro assay intracellular staining (ICS) were utilized assess dendritic cells (DCs) functions. assay, proliferation...
Background: Respiratory syncytial virus (RSV) vaccine is an unmet medical need. The reduction neutralization test (VRNT) was developed to replace the LI-COR microneutralization assay measure RSV titers. Methods: A bridging study using selected V171 phase I samples and calibration studies WHO international standard antiserum were performed compare VRNT LI-COR. Results: From study, we showed good concordance between titers, similar post-/prevaccination titer ratios. studies, can convert titers...
An attenuated West Nile virus (WNV), a nonstructural (NS) 4B-P38G mutant, induced higher innate cytokine and T cell responses than the wild-type WNV in mice. Recently, myeloid differentiation factor 88 (MyD88) signaling was shown to be important for initial priming memory development during NS4B-P38G mutant infection. In this study, two flow cytometry-based methods – an vitro assay intracellular staining (ICS) were utilized assess dendritic cells (DCs) functions. assay, proliferation...
Abstract West Nile virus (WNV)- induced neurological disease has become a public health concern. No vaccines have been approved for human use. We previously shown that an attenuated WNV, the nonstructural (NS) 4B-P38G mutant, stronger innate cytokine and T cell responses than wild-type WNV. Mice immunized with this mutant were all protected from subsequent lethal WNV infection. Here, we found both Toll-like receptor (TLR7) MyD88 expression are required host protection NS4B P38G Infected...