A5080624318- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- Glycosylation and Glycoproteins Research
- Particle accelerators and beam dynamics
- Nuclear Physics and Applications
- SARS-CoV-2 and COVID-19 Research
- Cytomegalovirus and herpesvirus research
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Immunology Research
- RNA Interference and Gene Delivery
- Particle Accelerators and Free-Electron Lasers
- Immunodeficiency and Autoimmune Disorders
- Blood groups and transfusion
- Advanced Chemical Physics Studies
- Superconducting Materials and Applications
- Laser-Matter Interactions and Applications
- COVID-19 Clinical Research Studies
- Power System Optimization and Stability
- Chemical Reactions and Isotopes
- Energy Load and Power Forecasting
- Animal Virus Infections Studies
Emory University
2022-2025
Dominion (United States)
2014-2024
Scripps Research Institute
2013-2023
Emory National Primate Research Center
2022
University of East Anglia
2001-2019
University of Washington
2019
Smiths Power (United States)
2014-2016
Harvard University
2011-2014
Commonwealth of Virginia
2014
Pennsylvania State University
2010-2011
Most simian-human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding CD4 (rhCD4) limits virus entry and replication could be enhanced by substituting naturally occurring simian residues at position 375, which resides a critical location in the CD4-binding pocket is under strong positive evolutionary pressure across broad spectrum of primate lentiviruses. SHIVs...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme (ACE2). ACE2 is also the viral receptor SARS-CoV (SARS-CoV-1), a related that emerged in 2002–2003. Horseshoe bats (genus Rhinolophus ) are presumed to be original reservoir both viruses, and SARS-like coronavirus, RaTG13, closely SARS-CoV-2, has been identified one horseshoe-bat species. Here we characterize ability S-protein...
An insect virus gene controls the behavior of dying host to increase dispersion virus.
When high intensity (≥1019 W cm−2) laser light interacts with matter, multi-MeV electrons are produced. These can be utilized to generate a MeV bremsstrahlung x-ray emission spectrum as they propagate into high-Z solid target positioned behind the interaction area. The short duration (<10 ps) and small diameter (<500 μm) of pulse combined offers an interesting alternative conventional sources based on electron accelerator used radiograph dense, rapidly moving objects. In...
The cytoplasmic tails of human and simian immunodeficiency virus (HIV SIV, respectively) envelope glycoproteins contain a highly conserved, membrane-proximal endocytosis motif that prevents the accumulation Env on surface infected cells prior to assembly. Using an assay designed measure killing virus-infected by antibody-dependent cell-mediated cytotoxicity (ADCC), we show substitutions in this increase susceptibility HIV-1- SIV-infected ADCC manner directly correlates with elevated levels...
Adeno-associated virus (AAV) delivery of potent and broadly neutralizing antibodies (bNAbs is a promising approach for the prevention HIV-1 infection. The immunoglobulin G (IgG)1 subtype usually selected this application, because it efficiently mediates antibody effector functions has somewhat longer half-life. However, use IgG1-Fc been associated with generation anti-drug (ADAs) that correlate loss expression. In contrast, we have shown expression antibody-like molecule eCD4-Ig bearing...
AAV-expressed eCD4-Ig protects rhesus macaques from SIVmac239.
An alternative to lifelong antiretroviral therapy (ART) is needed achieve durable control of HIV-1. Here, we show that adeno-associated virus (AAV) delivery two rhesus macaque antibodies the simian immunodeficiency (SIV) envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected barcoded SIV mac 239M after discontinuing suppressive ART. After AAV administration, sustained antibody expression minimal...
Due to its economical and environmental benefits society industry, integrating solar power is continuously growing in many utilities Independent System Operators (ISOs). However, the intermittent nature of renewable energy brings new challenges system operators. One key resolve this problem have a ubiquitously efficient output forecasting system, so as help enhance reliability, improve quality, achieve better generation scheduling formulate superior bidding strategies market. This paper...
Broadly neutralizing antibodies (bNAbs) can prevent and control an HIV-1 infection, but their breadth is invariably too limited for use as monotherapy. To address this problem, bi- trispecific antibody-like constructs have been developed. These engineered typically greater than the native bNAbs from which they were derived, are not more potent because do not, in most cases, simultaneously engage a single epitope of envelope glycoprotein (Env). Here, we describe new class bispecific targeting...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme (ACE2). ACE2 is also the viral receptor SARS-CoV (SARS-CoV-1), a related that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus ) are presumed to be original reservoir both viruses, and SARS-like coronavirus, RaTG13, closely SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize ability S-protein...
Barriers to effective gene therapy for many diseases include the number of modified target cells required achieve therapeutic outcomes and host immune responses expressed proteins. As long-lived specialized protein secretion, antibody-secreting B are an attractive foreign expression in blood tissue. To neutralize HIV-1, we developed a lentiviral vector (LV) platform delivery anti-HIV-1 immunoadhesin, eCD4-Ig, cells. The EμB29 enhancer/promoter LV limited non-B cell lineages. By engineering...
Lymantria dispar has a long historical association with the baculovirus multiple nucleopolyhedrovirus (LdMNPV), which is one of primary population regulators L. in field. However, host larvae exhibit strong developmental resistance to fatal infection by LdMNPV; LD50 newly moulted fourth instars 18-fold lower than middle instar (48–72 h post-moult). Using recombinant LdMNPV expressing lacZ, we examined key steps pathogenesis explore mechanisms resistance. At midgut level, observed reduced...
Antibody-dependent cell-mediated cytotoxity (ADCC) can eliminate HIV-1 infected cells, and may help reduce the reservoir of latent virus in patients. Sera positive individuals include a number antibodies that recognize epitopes usually occluded on envelope glycoprotein (Env) trimers. We have recently described eCD4-Ig, potent exceptionally broad inhibitor entry be used to protect rhesus macaques from multiple high-dose challenges with simian-human immunodeficiency AD8 (SHIV-AD8). Here we...
RNA switches that modulate gene expression with small molecules have a number of scientific and clinical applications. Here, we describe novel class regulatory on based the ability ligand-bound aptamer to promote stem formation between microRNA target sequence (miR-T) complementary competing strand. Two switch architectures employing this basic concept were evaluated, differing in location tetracycline region miR-21 (miR-21-T) masked by its Further optimizations miR-21-T strand resulted...
The human immunodeficiency virus type 1 (HIV-1) entry inhibitor eCD4-Ig is a fusion of CD4-Ig and coreceptor-mimetic peptide. markedly more potent than CD4-Ig, with neutralization efficiencies approaching those HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, neutralized all HIV-1, HIV-2, simian (SIV) isolates that it has been tested against, suggesting may be useful in clinical settings, where antibody escape concern. Here, we characterize three new variants, each...
The engineered antibody-like entry inhibitor eCD4-Ig neutralizes every human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian isolate it has been tested against. exceptional breadth of derives from its ability to closely simultaneously emulate the HIV-1 receptor CD4 coreceptors, either CCR5 or CXCR4. Here we investigated whether viral escape is more difficult than that CD4-Ig CD4-binding site antibody NIH45-46. We observed a swarm selected with high concentrations was increasingly...
A tyrosine-sulfated CCR5-mimetic peptide, CCR5mim1, inhibits HIV-1 infection more efficiently than sulfopeptides based on the CCR5 amino terminus. Here we characterized sulfopeptide chimeras of CCR5mim1 and heavy-chain CDR3 antibody PG16. Two bound a range envelope glycoproteins neutralized CCR5mim1. An immunoadhesin form one these, CCR5mim2-Ig, synergized with CD4-Ig to neutralize HIV-1. These are among broadest most potent peptides described date.
Many broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus type 1 (HIV-1) were shown effective in animal models, and are currently evaluated clinical trials. However, use of these humans is hampered by the rapid emergence resistant viruses. Here we show that soft-randomization can be used to accelerate parallel identification viral escape pathways. As a proof principle, soft-randomized epitope regions VRC01-class bNAbs replication-competent HIV-1 selected for variants....
Adeno-associated virus (AAV)-based gene therapies are emerging strategies in Duchenne muscular dystrophy (DMD) treatment. Exposure to wild-type AAV can lead development of neutralizing antibodies (NAbs) and blocking transduction, thereby limiting the delivery vector-based therapy. Therefore, it is imperative check for presence NAbs a patient who candidate We prospectively enrolled 101 genetically confirmed males with DMD (median age 11 years, 48% ambulatory 59% on steroids) performed...