A5078832087- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- Animal Disease Management and Epidemiology
- HIV-related health complications and treatments
- T-cell and Retrovirus Studies
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Vector-Borne Animal Diseases
- Pneumocystis jirovecii pneumonia detection and treatment
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Herpesvirus Infections and Treatments
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- Immune responses and vaccinations
- Viral gastroenteritis research and epidemiology
- Calcium signaling and nucleotide metabolism
- Tracheal and airway disorders
- Extracellular vesicles in disease
- Bacterial Identification and Susceptibility Testing
- Reproductive tract infections research
- Gut microbiota and health
- Immune Response and Inflammation
University of Louisiana at Lafayette
2019-2025
Tulane University
2013-2021
University of Nebraska Medical Center
2015-2018
RIKEN
2012-2016
University of Dundee
2014
The University of Tokyo
2012
National University of San Marcos
2010
Alveolar macrophages (AMs) obtained by bronchoalveolar lavage (BAL) are commonly used to study lung macrophage-mediated immune responses. Questions remain, however, about whether AMs fully represent macrophage function in the lung. This was performed determine contribution of interstitial (IMs) tissue pulmonary immunity and that not present BAL sampling. In vivo BrdU injection evaluate kinetics monocyte/tissue turnover Indian rhesus macaques (Macaca mulatta). Lung phenotype cell were...
mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling LNP/mRNA quantitative visualization trafficking in live mice and non-human primates (NHPs). Following intramuscular injection, observed LNPs distributing through injected muscle tissue, simultaneous with rapid to...
Bovine leukemia virus (BLV) is a member of retroviridae family, together with human T cell types 1 and 2 (HTLV-1 -2) belonging to the genes deltaretrovirus, infects cattle worldwide. Previous studies have classified env sequences BLV provirus from different geographic locations into eight genetic groups. To investigate variability in South America, we performed phylogenetic analyses whole genome partial gp51 strains isolated Peru, Paraguay Bolivia, for which no molecular characteristics...
Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such are not likely the solitary viral reservoir and as defining where how others is imperative for eradication measures. To ends, we used HIV-1ADA-infected NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice reconstituted with a immune system explore two long-acting ART regimens investigating their abilities affect cell...
Abstract HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model barcoded SIVmac239 intravenous infection and therapeutic dosing anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirm latency reversal properties vivo TGF-β blockade, decrease stimulate responses. Treatment eight female, SIV-infected macaques on with four 2-weeks cycles leads reactivation as indicated by plasma load immunoPET/CT a 64 Cu-DOTA-F(ab’)...
Abstract Humanized mice have emerged as a testing platform for HIV-1 pathobiology by reflecting natural human disease processes. Their use to study biology, virology, immunology, pathogenesis and therapeutic development has served robust alternative more-well developed animal models HIV/AIDS. A critical component in such rests defining the tissue cellular sites infection. To this end, we examined viral infection bone marrow, blood, spleens, liver, gut, brain, kidney lungs of CD34+...
Antiretroviral drug discovery and formulation design will facilitate viral clearance in infectious reservoirs. Although progress has been realized for selected hydrophobic integrase nonnucleoside reverse transcriptase inhibitors, limited success seen to date with hydrophilic nucleosides. To overcome these limitations, long-acting nanoparticles were created the commonly used nucleoside inhibitor, lamivudine (2',3'-dideoxy-3'-thiacytidine, 3TC).A 2-step synthesis a slow-release 3TC....
There is a clear need for low-cost, self-applied, long-lasting approaches to prevent human immunodeficiency virus (HIV) infection in both men and women, even with the advent of pre-exposure prophylaxis (PrEP). Broadly neutralizing antibodies represent an option improve HIV prophylaxis, but intravenous delivery, cold-chain stability requirements, low cervicovaginal concentrations, cost may preclude their use. Here, we present approach express anti-GP120 broadly antibody PGT121 primary site...
Tuberculosis (TB) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) profoundly affect the system synergistically accelerate disease progression. It is believed that CD4+ T-cell depletion by HIV major cause of reactivation latent TB. Previous studies demonstrated blood monocyte turnover concurrent with tissue macrophage death from infection better predicted AIDS onset than in macaques infected simian (SIV). In this study, we describe contribution macrophages to...
Long-acting nanoformulated antiretroviral therapy (nanoART) is designed to improve patient regimen adherence, reduce systemic drug toxicities, and facilitate clearance of human immunodeficiency virus type one (HIV-1) infection. While nanoART establishes depots within recycling late monocyte-macrophage endosomes, whether or not this provides a strategic advantage towards viral elimination has been elucidated.We applied quantitative SWATH-MS proteomics cell profiling nanoparticle atazanavir...
To our knowledge, this study demonstrates for the first time that AIDS virus differentially impacts two distinct subsets of lung macrophages. The predominant macrophages harvested by bronchoalveolar lavage (BAL), alveolar (AMs), are routinely used in studies on human macrophages, long-lived cells, and exhibit low turnover. Interstitial (IMs) inhabit tissue, not recovered with BAL, shorter-lived, higher baseline turnover rates from AMs. We examined effects SIV infection AMs BAL fluid IMs...
TGF-β plays a critical role in maintaining immune cells resting state by inhibiting cell activation and proliferation. Resting HIV-1 target represent the main cellular reservoir after long-term antiretroviral therapy (ART). We hypothesized that releasing from TGF-β–driven signaling would promote latency reversal. To test our hypothesis, we compared models with without type 1 receptor inhibitor, galunisertib. tested effect of galunisertib SIV-infected, ART-treated macaques monitoring SIV-env...
SUMMARY mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling LNP/mRNA quantitative visualization trafficking in live non-human primates (NHPs). Following i.m. injection, observed LNPs distributing through injected muscle tissue, simultaneous with rapid to draining...
Abstract Background Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis and closely related to human T-cell type I. The Tax protein of BLV a transcriptional activator viral replication key contributor oncogenic potential. We previously identified interesting mutant forms elevated (Tax D247G ) or reduced S240P transactivation effects on propagation. However, the these mutations functions other than activation are unknown. In this study, identify genes that play role in...
Human and bovine respiratory syncytial viruses (HRSV/BRSV) are major causes of severe lower tract infections in children calves, respectively. Shared epidemiological, clinical, pathological genetic characteristics these make comparative research highly relevant. To characterise the host response against BRSV infection, bronchoalveolar lavage supernatant (BAL) from i) non-vaccinated, BRSV-infected ii) vaccinated, iii) non-infected calves was analysed by tandem mass spectrometry. Proteins were...
During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown facilitate antiviral responses. Long-acting ritonavir-boosted atazanavir (nanoATV/r) nanoformulations co-administered with URMC-099 reduced viral load and numbers HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone humanized NOD/SCID/IL2Rγc-/- mice. The effects were...
While the therapeutic potential for current long-acting (LA) antiretroviral therapy (ART) is undeniable, ligand-decorated nanoformulated LA-ART could optimize drug delivery to viral reservoirs. The development of decorated ART hinges, however, on formulation processes and manufacture efficiencies. To this end, we compared purification techniques nanocrystals.Ligand-decorated nanoparticle manufacturing was tested using folic acid (FA) cabotegravir.Direct FA-cabotegravir resulted in stable...
Quantification of plasma viral load (PVL) is used to monitor disease progression in SIV-infected macaques. This study was aimed at optimizing performance characteristics the quantitative PCR (qPCR) PVL assay.The quantification procedure optimized by inclusion an exogenous control hepatitis C virus armored RNA (aRNA), a concentration step, extended digestion with proteinase K, and second elution step. Efficiency (vRNA) extraction compared using several commercial vRNA kits. Various parameters...
Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known dynamics nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, uptake distribution following both intraperitoneal intramuscular injection atazanavir (nanoATV). Local inflammatory responses heralded to...
Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) the form of secretory is most abundant antibody class mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy 64Cu-labeled, photoactivatable-GFP (PA-GFP-BaL) fluorescently labeled to determine how antibodies influence interaction with barriers viral penetration colorectal tissue. Our...
Abstract Background Human T cell leukemia virus type 1 (HTLV-1) Tax is a potent activator of viral and cellular gene expression that interacts with number proteins. Many reports show capable regulating cycle progression apoptosis both positively negatively. However, it still remains to understand why the oncoprotein induces arrest apoptosis, or whether Tax-induced dependent upon its ability induce G arrest. The present study used time-lapse imaging explore spatiotemporal patterns dynamics in...