A5067136189- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Neuroinflammation and Neurodegeneration Mechanisms
- HIV-related health complications and treatments
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- Hepatitis C virus research
- Tryptophan and brain disorders
- Health Systems, Economic Evaluations, Quality of Life
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- Ion channel regulation and function
- Mosquito-borne diseases and control
- Blood groups and transfusion
- Hepatitis Viruses Studies and Epidemiology
- Virology and Viral Diseases
- Biochemical Analysis and Sensing Techniques
- Pneumocystis jirovecii pneumonia detection and treatment
- Hepatitis B Virus Studies
- Neuroscience and Neuropharmacology Research
- Viral Infections and Immunology Research
National Institute of Allergy and Infectious Diseases
2017-2025
Universidade Nove de Julho
2025
Johns Hopkins Medicine
2015-2024
Johns Hopkins University
2015-2024
National Institutes of Health
2019-2024
Massachusetts Institute of Technology
2022
St Clements University Higher Education School
2022
Creative Commons
2022
Administração Regional de Saúde de Lisboa e Vale do Tejo
2021
Institut de Recherche Vaccinale
2021
The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies purge these reservoirs are needed and activation viral gene expression one promising strategy. Bromodomain Extraterminal (BET) bromodomain inhibitors (BETi) compounds able reactivate latent proviruses positive transcription elongation factor b (P-TEFb)-dependent manner. In this study, we tested the reactivation potential protein kinase C...
The development of persistent cellular reservoirs latent human immunodeficiency virus (HIV) is a critical obstacle to viral eradication since rebound takes place once anti-retroviral therapy (ART) interrupted. Previous studies show that HIV persists in myeloid cells (monocytes and macrophages) blood tissues virologically suppressed people with (vsPWH). However, how contribute the size reservoir what impact they have on after treatment interruption remain unclear. Here we report...
Abstract HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb may be needed for robust suppression of viremia. We performed two-part study consisting single-center, randomized, double-blind, dose-escalation, placebo-controlled first-in-human trial the V2-glycan-specific antibody PGDM1400 alone in combination V3-glycan-specific PGT121 24 adults without HIV part 1, as well multi-center, open-label PGDM1400, and...
Expression of Ca 2+ -sensing receptors (CaR) was demonstrated in several human intestinal epithelial cell lines (T84, HT-29, and Caco-2) rat epithelium by both reverse transcriptase-polymerase chain reaction (PCR) Northern blotting RNA. Restriction patterns the PCR products were sizes predicted sequences. CaR agonists (Ca , poly-l-arginine, protamine) mediated an increase intracellular HT-29–18-C1 cells (monitored changes fura 2 fluorescence), which dependent on release from...
IFN-beta production is an inaugural event in the innate immune response to viral infections, with relatively small fold changes expression resulting activation of important antiviral signaling cascades. In our rapid SIV/macaque model HIV encephalitis, virus enters CNS within 4 d infection, accompanied by a marked that wanes as SIV replication controlled. The centrality combines potential inflammatory damage associated long-term this pathway suggest may be subject regulatory fine-tuning...
ABSTRACT The treatment of human immunodeficiency virus type 1 (HIV-1) infection with highly active antiretroviral therapy (HAART), a combination three or more drugs, suppresses viremia below the clinical limit detection (50 HIV-1 RNA copies/ml), but latently infected resting CD4 + T cells serve as lifelong reservoirs, and low-level can be detected special assays. Recent studies have provided evidence for additional reservoirs that contribute to residual are not present in circulating cells....
A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation neuronal damage cerebrospinal fluid (CSF) demonstrate continued effects HIV brain suggest central nervous system (CNS) may serve as a...
Objective: Resting CD4+ T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an simian immunodeficiency virus (SIV)/macaque model for AIDS and HIV-related neurocognitive disorders we assessed contribution brain to viral latency reactivation. Design: Pigtailed macaques were dual inoculated with SIVDeltaB670 SIV17E-Fr treated efficacious central nervous system-penetrant ART. After 500 days suppression animals two cycles reversing...
HIV reservoirs persist despite antiretroviral therapy (ART) and are established within a few days after infection. Infected myeloid cells in the central nervous system (CNS) may contribute to establishment of CNS viral reservoir. The mature CD14+ CD16+ monocyte subset enters response chemokines, including CCL2. Entry infected monocytes lead infection other cells, macrophages or microglia astrocytes, release neurotoxic early proteins additional cytokines. This contributes neuroinflammation...
Despite the success of combined antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains a lifelong because latent viral reservoirs in infected patients. The contribution CD4(+) T cells to and disease progression has been extensively studied. However, during early HIV infection, macrophages brain other tissues are contribute tissue-specific diseases, such as encephalitis dementia pneumonia lung. extent monocytes not rigorously assessed with assays comparable those...
Human induced pluripotent stem cells (iPSCs), together with 21st century cell culture methods, have the potential to better model human physiology, applications in toxicology, disease modeling, and study of host-pathogen interactions. Several models brain been developed recently, demonstrating cell-cell interactions multiple types physiologically relevant 3D structures. Most current models, however, lack ability represent inflammatory response because they do not include a microglial...
Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding all viral reservoirs that could contribute to rebound after ART interruption. CD4 T cells (CD4s) are recognized as predominant reservoir HIV type 1 (HIV-1)-infected individuals. However, macrophages also infected by HIV-1 and simian (SIV) during acute infection may persist throughout ART, contributing size latent reservoir. We sought determine...
Treatment of HIV infection with either antiretroviral (ARV) therapy or neutralizing monoclonal antibodies (NAbs) leads to a reduction in plasma virus. Both ARVs and NAbs prevent new rounds viral infection, but may have the additional capacity accelerate loss virus-infected cells through Fc gamma receptor (FcγR)-mediated effector functions, which should affect kinetics plasma-virus decline. Here, we formally test role function vivo by comparing rate timing clearance response single-dose...
Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and have immunotherapeutic effects against reservoirs. We conducted a prospective clinical trial with two bNAbs (VRC01LS 10-1074) in children ( n = 25) who had previously initiated small-molecule ART before 7 days of age continued at least 96 weeks. Both were dosed intravenously every 4 weeks, overlapping 8 weeks then up 24 or until detectable...
Calcium sensing (CaR) and Group I metabotropic glutamate receptors exhibit overlapping expression patterns in brain, share common signal transduction pathways. To determine whether CaR (mGluRs) (mGluR1α mGluR5) can form heterodimers, we immunoprecipitated from bovine brain observed co-precipitation of mGluR1α. mGluR1α co-localize hippocampal cerebellar neurons, but are expressed separately other regions. <i>In vitro</i> transfection studies HEK-293 cells established the specificity...
A homology model for the human calcium sensing receptor (hCaR) transmembrane domain utilizing bovine rhodopsin (bRho) structural information was derived and tested by docking allosteric antagonist, NPS 2143, followed mutagenesis of predicted contact sites. Mutation residues Phe-668 (helix II), Arg-680, or Phe-684 III) to Ala (or Val Leu) Glu-837 VII) Ile Gln) reduced inhibitory effects 2143 on [Ca2+]i responses. The calcimimetic R-568 increases potency Ca2+ in functional assays CaR....
Background. During the era of highly active antiretroviral therapy (HAART), prevalence HIV-associated central nervous system (CNS) disease has increased despite suppression plasma viremia. Methods. In a simian immunodeficiency virus (SIV) model in which all animals develop AIDS and 90% CNS by 3 months after inoculation, pigtailed macaques were treated with regimen tenofovir disoproxil fumarate, saquinavir, atazanavir, an integrase inhibitor starting at 12 days inoculation euthanized ∼175...
Central nervous system (CNS) invasion during acute-stage HIV-infection has been demonstrated in a small number of individuals, but there is no evidence neurological impairment at this stage and virus infection brain appears to be controlled until late-stage disease. Using our reproducible SIV macaque model examine the earliest stages CNS, we identified immune responses that differentially regulate inflammation replication compared peripheral blood lymphoid tissues. macrophages SIV-infected...
HIV infection is not cleared by antiretroviral drugs due to the presence of latently infected cells that are eliminated with current therapies and persist in blood organs patients. New compounds activate these latent reservoirs have been evaluated so that, along HAART, they can be used virus eliminate resulting eradication viral infection. Here we describe three novel diterpenes isolated from sap Euphorbia tirucalli, a tropical shrub. These molecules, identified as ingenols, were modified at...
Understanding the cellular and anatomical sites of latent virus that contribute to human immunodeficiency (HIV) rebound is essential for eradication. In HIV-positive patients, CD4+ T lymphocytes comprise a well-defined functional reservoir, defined as cells containing transcriptionally silent genomes able produce infectious once reactivated. However, persistence in compartments other than blood lymph nodes unclear. Macrophages (Mϕ) are infected by HIV/simian (SIV) likely carry viral during...
A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence persistently infected cells that establish a long-lived viral reservoir. largely resides in anatomical regions are inaccessible routine sampling, however, and non-invasive methods understand longitudinal tissue-wide burden persistence urgently needed. Positron emission tomography (PET) imaging promising strategy identify characterize HIV. Here, we assess efficacy...
Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in fragment crystallizable region to improve pharmacokinetic profiles. The mutation delays antibody clearance by enhancing binding affinity neonatal receptor found on endothelial cells. To characterize for monoclonal targeting HIV, we compared parameters between parental versus variants five pairs anti-HIV immunoglobin G1 (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS...