A5012117747- Herpesvirus Infections and Treatments
- Respiratory viral infections research
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Cytomegalovirus and herpesvirus research
- Bacillus and Francisella bacterial research
- Bacteriophages and microbial interactions
- Viral Infections and Vectors
- Viral Infections and Immunology Research
- Viral Infectious Diseases and Gene Expression in Insects
- Plant Virus Research Studies
- RNA regulation and disease
- Animal Virus Infections Studies
- Viral Infections and Outbreaks Research
- Antibiotic Resistance in Bacteria
- Animal Disease Management and Epidemiology
- Advanced materials and composites
- RNA and protein synthesis mechanisms
- Microbial infections and disease research
- Hepatitis C virus research
- Vector-Borne Animal Diseases
- Immune Cell Function and Interaction
- Bacterial Identification and Susceptibility Testing
- Semiconductor materials and devices
- Yersinia bacterium, plague, ectoparasites research
United States Food and Drug Administration
2021-2024
United States Naval Research Laboratory
2020-2024
United States Department of Homeland Security
2009-2023
Palmetto General Hospital
2023
Center for Food Safety and Applied Nutrition
2019-2021
Pacific Northwest National Laboratory
2021
Battelle
2021
Sharma & Associates (United States)
2021
EcoHealth Alliance
2021
Booz Allen Hamilton (United States)
2019-2020
The death toll and economic loss resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are stark reminders that we vulnerable to zoonotic viral threats. Strategies needed identify characterize animal viruses pose greatest risk of spillover spread in humans inform public health interventions. Using expert opinion scientific evidence, identified host, viral, environmental factors contributing virus humans. We then developed a ranking framework interactive web...
Abstract Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90% of cases both humans and nonhuman primates. No vaccines or treatments are available for human use. We evaluated the effects primates vaccine strategies had protected mice guinea pigs from lethal EBOV infection. The following immunogens were used: RNA replicon particles derived an attenuated strain Venezuelan equine encephalitis (VEEV) expressing glycoprotein nucleoprotein; recombinant Vaccinia glycoprotein;...
Previous reports have established that vaccinia virus (VV) recombinants expressing G, F, or N protein of respiratory syncytial (RS) protect small animals against intranasal challenge with live RS virus. This work demonstrates a variety parameters affect the protection induced by recombinant viruses. The route vaccination, subtype virus, and species used influenced antibody titers extent protection. During these studies, observations were also made on subclass generated, pulmonary...
Phosphorothioate oligonucleotides complementary to mRNA of the human cytomegalovirus (HCMV) DNA polymerase gene or RNA transcripts major immediate-early regions 1 and 2 (IE1 IE2) HCMV were evaluated for antiviral activity in a 96-well immunoassay with primary dermal fibroblasts as host cells. Oligonucleotides IE2 region exhibited most potent activity. One these oligonucleotides, ISIS 2922, was at least 30-fold more than nucleoside analog, ganciclovir, 50% effective concentration 0.37 microM...
ISIS 2922 is a phosphorothioate oligonucleotide that complementary to human cytomegalovirus (CMV) immediate-early (IE) RNA and exhibits potent specific antiviral activity against CMV in cell culture assays. Specific assay systems were developed separately characterize the antisense nonantisense components of mediated by 2922. In U373 cells transformed with cDNA encoding IE 55-kDa (IE55) protein, expression was inhibited at nanomolar concentrations comparable effective The specificity...
The herpes simplex virus type 1 latency-associated transcript (LAT) is expressed as a major species 2,100 to 2,200 bases in length and less abundant one ca. 730 shorter latently infected mouse rabbit neurons. RNA blot hybridization experiments using 20- 22-base synthetic oligonucleotides mung bean nuclease protection assays have demonstrated that the smaller LAT colinear with larger one, except for 730-base intron. On basis of Northern analysis, spliced which comprises much 50% total latent...
We examined the human cytotoxic T-cell repertoire of nine adults to 9 10 proteins respiratory syncytial (RS) virus. Peripheral blood mononuclear cells from normal were stimulated with RS virus in vitro. The resulting polyclonal cultures tested for lysis B-lymphoblastoid cell lines infected recombinant vaccinia viruses expressing each individual proteins. use peripheral dendritic present antigen gave more easily reproducible results over a shorter culture period than conventional methods. six...
Vaccinia virus (VV) recombinants were constructed that contained full-length cDNA copies of the fusion (F) protein gene human respiratory syncytial (RS) virus. The F was placed next to strong early-late VV 7.5-kilodalton promoter and located within thymidine kinase (tk) gene. Full-length recombinant transcripts initiated at both tk promoters accumulated in cells early infection, one or more these translated yield a glycoprotein which comigrated with Fo, precursor. This precursor processed by...
We used herpes simplex virus type 1 (HSV-1) DNA and restriction fragments of HSV-1 covalently coupled to cellulose as a reagent isolate for further characterization the major minor immediate-early mRNA species in HeLa cells infected maintained absence de novo protein synthesis. Five several were characterized. One was 4.2-kilobase mapping TR S /IR region with its 3′ end distal U region; this encoded 170,000-dalton polypeptide vitro. A 2.8-kilobase mRNA, encoding 120,000-dalton polypeptide,...
The emergence and dissemination of carbapenemases, bacterial enzymes able to inactivate most β-lactam antibiotics, in Enterobacteriaceae is increasing concern. concurrent spread resistance against colistin, an antibiotic last resort, further compounds this challenge further. Whole-genome sequencing (WGS) can play a significant role the rapid accurate detection/characterization existing emergent determinants, essential aspect public health surveillance response activities combat antimicrobial...
Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide translation HCV directed by an internal ribosome entry site (IRES) located within NCR. We investigated inhibition gene expression using antisense oligonucleotides complementary to NCR, initiation codon, core protein coding sequences. Oligonucleotides were evaluated for activity after treatment a human hepatocyte...
Recombinant vaccinia viruses containing the 22-kilodalton protein (matrixlike or 22K protein) phosphoprotein gene from respiratory syncytial virus were constructed. These recombinant expressed proteins which immunoprecipitated by appropriate antibodies and comigrated with authentic produced infection. The new (and others previously described attachment glycoprotein, fusion, nucleoprotein genes of virus) used to infect target cells for cultured polyclonal cytotoxic T lymphocytes generated...
ABSTRACT A human cytomegalovirus mutant that was isolated for resistance (10-fold) to the antisense oligonucleotide fomivirsen (ISIS 2922) exhibited cross-resistance a modified derivative of with an identical base sequence but little or no unrelated sequence. No changes in mutant’s DNA corresponding target were found.
We have isolated as recombinant DNA clones, in the plasmid pBR322, regions of herpesvirus type 1 genome spanning region between 0.53 and 0.6 on prototypical arrangement. This 11,000-base-pair corresponds to 10% large unique encodes five major several minor mRNA species abundant at different times after infection, which range length from 7 kilobase. In this report, we used RNA transfer blots S1 nuclease digestion hybrids viral polyribosomal precisely localize (+/- 0.1 kilobase) these mRNA's....
We have used DNA bound to cellulose isolate and translate in vitro herpes simplex virus type 1 (HSV-1) mRNA's encoded by HindIII fragment L (mapping between 0.592 0.647), 8.450-base-pair (8.45-kb) portion of the long unique region viral genome. Readily detectable, late 2.7 1.9 kb size encoding 69,000- 58,000-dalton polypeptides, respectively, were isolated. A very minor mRNA family composed two colinear forms, one 2.6 2.8 kb, was isolated found encode only an 85,000-dalton polypeptide. major...
We examined the genetic and antigenic properties of Dobrava (DOB) virus, a hantavirus associated with severe haemorrhagic fever renal syndrome in Europe. Cloning sequence analyses revealed DOB M segment to consist 3644 nucleotides, coding capacity 1134 amino acids virus complementary-sense RNA (cRNA). Seven potential asparagine-linked glycosylation sites were identified gene product, one G2 six G1 regions. The S is 1667 nucleotides long, has single ORF cRNA capable encoding protein 428...
Bovine respiratory syncytial (BRS) virus causes a severe lower tract disease in calves similar to the children caused by human (HRS) virus. While there is antigenic cross-reactivity among other major viral structural proteins, glycoprotein, G, of BRS and that HRS are antigenically distinct. The G glycoprotein has been implicated as attachment protein for We have carried out molecular comparison with counterparts. cDNA clones corresponding mRNA were isolated analyzed dideoxynucleotide...
Human adenovirus type 5 (Ad5) is a DNA virus which replicates as efficiently in human A549 cells treated with interferon-alpha 2 (IFN) untreated cells. Vesicular stomatitis (VSV), on the other hand, negative-strand RNA very sensitive to effects of IFN treatment The IFN-mediated inhibition VSV replication was not observed coinfected Ad5. Abrogation antiviral activity maximal when Ad5 infection preceded by at least 36 h, but did require synthesis for manifestation. Coinfection experiments and...
The major glycoprotein, G, of human respiratory syncytial (RS) virus is a Mr 84,000-90,000 species that has about 60% its mass contributed by carbohydrate, most which in the form O-linked oligosaccharides. G protein contains neither hydrophobic N-terminal signal sequence nor C-terminal anchor region. Instead, amino acid reveals only one region with significant character, between residues 38 and 66. In order to study synthesis, processing, functions this unusual viral full-length cDNA copies...
Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. Current treatments are not curative for most infected individuals, and there an urgent need both novel therapeutic agents small-animal models which can be used to evaluate candidate drugs. A model HCV gene expression was developed with recombinant vaccinia vectors. VHCV-IRES (internal ribosome entry site) a viral vector containing 5' nontranslated region (5'-NTR) portion core coding fused firefly luciferase gene....
Combinatorial strategies offer the potential to generate and screen extremely large numbers of compounds identify individual molecules with a desired binding specificity or pharmacological activity. We describe combinatorial strategy for oligonucleotides in which library is generated screened without using enzymes. Freedom from enzymes enables use oligonucleotide analogues. This dramatically extends scope both targets that may be screened. demonstrate utility method by screening 2'-O-Methyl...