A5061798289- Rabies epidemiology and control
- Viral Infections and Outbreaks Research
- Virology and Viral Diseases
- Viral Infections and Vectors
- Poxvirus research and outbreaks
- Hepatitis B Virus Studies
- Virus-based gene therapy research
- HIV Research and Treatment
- Microbial infections and disease research
- Bacillus and Francisella bacterial research
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Venomous Animal Envenomation and Studies
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Animal Virus Infections Studies
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- Immune Cell Function and Interaction
- Polymer crystallization and properties
- Influenza Virus Research Studies
- Material Dynamics and Properties
- Viral gastroenteritis research and epidemiology
- COVID-19 epidemiological studies
- T-cell and B-cell Immunology
Thomas Jefferson University
2015-2024
United States Army Medical Research Institute of Infectious Diseases
2023
Bridge University
2023
Sidney Kimmel Cancer Center
2006-2022
Philadelphia University
2001-2015
Fox Chase Cancer Center
2015
National Institutes of Health
2014
Temple University Hospital
2008
Amgen (United States)
2008
University of Pennsylvania
2002-2008
In a previous study we demonstrated that vesicular stomatitis virus (VSV) can be used as vector to express soluble protein in mammalian cells. Here have generated VSV recombinants four different membrane proteins: the cellular CD4 protein, CD4-G hybrid containing ectodomain of and transmembrane cytoplasmic tail glycoprotein (G), measles hemagglutinin, or fusion protein. The proteins were expressed at levels ranging from 23-62% G all transported cell surface. addition found incorporated into...
A new transcription unit was generated in the 3' noncoding region of vesicular stomatitis virus (VSV) glycoprotein gene by introducing smallest conserved sequence found at each VSV junction. This introduced into a DNA copy genome from which infectious can be derived. It contained an 11-nucleotide putative stop/polyadenylation signal for mRNA, intergenic dinucleotide, and 10-nucleotide start preceding downstream foreign encoding bacterial enzyme chloramphenicol acetyltransferase. Infectious...
We describe a recombinant vesicular stomatitis virus lacking its glycoprotein gene and expressing instead the HIV-1 receptor CD4 coreceptor, CXCR4. This was unable to infect normal cells but did infect, propagate on, kill that were first infected with therefore had HIV membrane fusion protein on their surface. Killing of HIV-1-infected controlled infection in T cell line reduced titers infectious culture by as much 10(4)-fold. Such targeted could have therapeutic value reducing viral load....
ABSTRACT A recombinant rabies virus (RV) carrying two identical glycoprotein (G) genes (SPBNGA-GA) was constructed and used to determine the effect of RV G overexpression on cell viability immunity. Immunoprecipitation analysis flow cytometry showed that tissue culture cells infected with SPBNGA-GA produced, average, twice as much only a single gene (SPBNGA). The in SPBNGA-GA-infected NA paralleled by significant increase caspase 3 activity followed marked decrease mitochondrial respiration,...
ABSTRACT The matrix (M) proteins of vesicular stomatitis virus (VSV) and rabies (RV) play a key role in both assembly budding progeny virions. A PPPY motif (PY or late-budding domain) is conserved the M VSV RV. These PY motifs are important for mediating interactions with specific cellular containing WW domains. flanking sequences protein were used as bait to screen mouse embryo cDNA library interactors. Nedd4 protein, membrane-localized ubiquitin ligase multiple domains, was identified from...
Ab initio methods are used for investigating structural and electronic properties of silicon−carbon nanotubes (SiCNTs). Tubes with different Si to C ratios were tested the trend from C-rich Si-rich SiCNTs is examined. Our results show that lose stability when ratio over increases. Nevertheless they remain stable until reaches 50:50, after tubes collapse nanowires or clusters solid interiors. The density states also presented analyzed.
ABSTRACT Several rabies virus (RV) vaccine strains containing an aspartic acid (Asp) or glutamic (Glu) instead of arginine (Arg) at position 333 the RV glycoprotein (G) are apathogenic for immunocompetent mice even after intracranial inoculation. However, we previously showed that nonpathogenic phenotype highly attenuated strain SPBNGA, which contains a Glu G, is unstable when this passaged in newborn mice. While remained unchanged five mouse passages, Asn 194 →Lys mutation occurred G. This...
Rabies is a zoonotic disease that remains an important public health problem worldwide and causes more than 70,000 human deaths each year. The causative agent of rabies virus (RV), negative-stranded RNA the rhabdovirus family. Neuroinvasiveness neurotropism are main features define pathogenesis rabies. Although RV pathogenicity multigenic trait involving several elements genome, glycoprotein plays major role in by controlling rate uptake trans-synaptic spread, regulating replication....
We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy these live RABV/EBOV vaccines. Here, we evaluated vaccines in nonhuman primates. Our results indicate that all three do induce potent immune responses against both EBOV, while...
Abstract Lassa fever (LF), caused by virus (LASV), is a viral hemorrhagic for which no approved vaccine or potent antiviral treatment available. LF WHO priority disease and, together with rabies, major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV rabies candidate (LASSARAB) that expresses codon-optimized glycoprotein (coGPC) adjuvanted TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against RABV both...
ABSTRACT Budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by subversion host proteins, such as Nedd4 E3 ubiquitin ligase, viral PPxY late (L) budding domains expressed within the matrix proteins these RNA viruses. As L are important for highly conserved in a wide array viruses, they represent potential broad-spectrum targets development antiviral drugs. To identify competitive blockers, we used known WW domain-PPxY interaction interface basis an silico screen. Using...
Proteins entirely expressed from cDNA were used to rescue synthetic RNA genome analogs into infectious defective particles of rabies virus (RV). Synthetic negative-stranded RNAs containing 3'- and 5'-terminal RV sequences transcriptional signal transcribed plasmids transfected cells expressing T7 polymerase recombinant vaccinia virus. After simultaneous expression N, P, L proteins a promoter, the genomes encapsidated, replicated, by proteins. Insertion bacterial chloramphenicol...
A reverse genetics approach was applied to generate a chimeric nonsegmented negative strand RNA virus, rabies virus (RV) of the Rhabdoviridae family, that expresses foreign protein. DNA constructs containing entire open reading frame bacterial chloramphenicol acetyltransferase (CAT) gene and an upstream RV cistron border sequence were inserted either into nontranslated pseudogene region full-length cDNA copy genome or exchanged with region. After intracellular T7 polymerase-driven expression...
Attenuated tissue culture-adapted and natural street rabies virus (RV) strains differ greatly in their neuroinvasiveness. To identify the elements responsible for ability of an RV to enter CNS from a peripheral site cause lethal neurological disease, we constructed full-length cDNA clone silver-haired bat-associated (SHBRV) strain 18 exchanged genes encoding proteins genomic sequences this highly neuroinvasive with those attenuated nonneuroinvasive vaccine (SN0). Analysis recombinant (SB0),...
Recent studies indicate that the interaction between rabies virus (RV) phosphoprotein and dynein light chain 8 (LC8) is essential for RV pathogenesis. Through its association with motor complex, LC8 has been suggested as a molecular factor links viral ribonucleoprotein to host cell transport system. structural investigations, however, dispute this model. To understand role of in pathogenesis, we generated recombinant RVs or without binding domain (LC8-BD) deleted from phosphoprotein....
As with many viruses, rabies virus (RABV) infection induces type I interferon (IFN) production within the infected host cells. However, RABV has evolved mechanisms by which to inhibit IFN in order sustain infection. Here we show that of dendritic cells (DC) potent and DC activation. Although DCs are RABV, viral replication is highly suppressed DCs, rendering non-productive. We exploited this finding bone marrow derived (BMDC) differentiate pattern recognition receptor(s) (PRR) responsible...
Survival of rabies virus–infected neurons depends on a single amino acid in the PDZ-binding site viral protein.
ABSTRACT The search for a safe and efficacious vaccine Ebola virus continues, as no current candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, (iii) chemically inactivated rabies (RABV) vaccines expressing Zaire (ZEBOV) glycoprotein (GP) by reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP efficiently expressed these candidates incorporated into virions. were avirulent after inoculation of adult mice, viruses...