A5066222547- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- Diabetes Management and Research
- Diabetes and associated disorders
- Epigenetics and DNA Methylation
- Pneumocystis jirovecii pneumonia detection and treatment
- Preterm Birth and Chorioamnionitis
- Genomics and Chromatin Dynamics
- Hepatitis C virus research
- Microbial Inactivation Methods
- COVID-19 Impact on Reproduction
- Pancreatic function and diabetes
- Reproductive System and Pregnancy
University of Pennsylvania
2019-2024
California University of Pennsylvania
2024
University of Washington
2015-2022
Penn Center for AIDS Research
2022
The transcription factor TOX is not exclusively linked to T cell exhaustion (see related Focus by Utzschneider and Kallies).
Elite control of HIV replication is linked to polyfunctional lymphoid CD8 + T cells that lack overt cytolytic activity and home B cell follicles.
Abstract Understanding the complexity of long-lived HIV reservoir during antiretroviral therapy (ART) remains a considerable impediment in research towards cure for HIV. To address this, we developed single-cell strategy to precisely define unperturbed peripheral blood HIV-infected memory CD4 + T cell from ART-treated people living with (ART-PLWH) via presence integrated accessible proviral DNA concert epigenetic and surface protein profiling. We identified profound heterogeneity within...
A primary obstacle for HIV elimination is the long-term viral reservoir in lymphoid tissues (LT) that can cause rebound viremia if therapy stopped. Cytotoxic CD8+ T cells are critical control of and SIV viremia; however, migrate to LT primarily non-cytotoxic, calling into question whether these could reduce on ART or replication when halted. To determine inhibit retained tissues, we inhibited lymphocyte egress from LTs antiretroviral (ART)-treated SIV-infected rhesus macaques (RM) during...
There is an urgent need for safe and effective antiretroviral therapy (ART) human immunodeficiency virus type 2 (HIV-2) infection. We undertook the first clinical trial of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) to assess its effectiveness in HIV-2-infected individuals Senegal, West Africa.HIV-2-infected, ART-naive adults with World Health Organization stage 3-4 disease or CD4 count <750 cells/μL were eligible this...
We compared the activity of integrase inhibitor bictegravir against HIV-1 and HIV-2 using a culture-based, single-cycle assay. Values 50% effective concentrations ranged from 1.2 to 2.5 nM for 9 isolates 1.4 5.6 15 isolates. mutants G140S/Q148R G140S/Q148H were 34- 110-fold resistant bictegravir, respectively; other resistance-associated mutations conferred ≤5-fold changes in susceptibility. Our findings indicate that bictegravir-based antiretroviral therapy should be evaluated...
The integration of HIV DNA into the host genome contributes to lifelong infection in most individuals. Few studies have examined lymphoid tissue, where predominantly persists before and after antiretroviral treatment (ART). Of particular interest is whether site distributions differ between stages with paired blood tissue comparisons. Here, we profiled sorted memory, tissue-resident, and/or follicular helper CD4+ T cell subsets from samples acute, chronic, ART-treated We observed minor...
There is a pressing need to identify more effective antiretroviral drugs for HIV-2 treatment. Here, we show that the investigational compound MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) highly active against group A and B isolates of HIV-2; 50% concentrations [EC50] were, on average, 4.8-fold lower than those observed HIV-1. also retains potent activity multinucleoside-resistant mutants (EC50 ≤ 11 nM). These data suggest may have antiviral in HIV-2-infected individuals.
We examined the antiviral activity of integrase inhibitor (INI) cabotegravir against HIV-2 isolates from INI-naive individuals. was sensitive to in single-cycle and spreading-infection assays, with 50% effective concentrations (EC 50 s) low subnanomolar range; comparable results were obtained for HIV-1 both assay formats.
Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and reduced susceptibility HIV-2 several protease (PIs) used in antiretroviral therapy (ART). In an effort identify new antiretrovirals treatment, we evaluated vitro activity investigational nucleoside analog BMS-986001 (2',3'-didehydro-3'-deoxy-4'-ethynylthymidine; also known as censavudine,...
Abstract Background Programmatic treatment outcome data for people living with human immunodeficiency virus type 2 (HIV-2) in West Africa, where the is most prevalent, are scarce. Methods Adults HIV-2 initiating or receiving antiretroviral therapy (ART) through Senegalese national AIDS program were invited to participate this prospective, longitudinal observational cohort study. We analyzed viral loads, CD4 cell counts, drug resistance, loss follow-up, and mortality. also examined changes...
Integrase inhibitors (INIs) are a key component of antiretroviral therapy for human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. Although INI resistance pathways well-defined HIV-1, mutations that emerge in response to INIs incompletely characterized.We performed systematic searches GenBank drug literature identify treatment-associated phenotypic evaluation. We then constructed library 95 mutants HIV-2ROD9 contained single or multiple amino acid changes the integrase protein. Each...
ABSTRACT Lymphocyte migration is essential for human adaptive immune surveillance. However, our current understanding of this process rudimentary, because most studies to date have been restricted immunological analyses blood and various tissues. To address issue, we used an integrated approach characterize tissue-emigrant cells in thoracic duct lymph (TDL). In humans non-human primates, lymphocytes were by far the abundant lineage population efferent lymph, a vast majority these T cells....
Extracellular signals are transmitted through kinase cascades to modulate gene expression, but it remains unclear how epigenetic changes regulate this response. Here, we provide evidence that growth factor-stimulated in the transcript levels of many responsive genes accompanied by increases histone phosphorylation levels, specifically at H3 serine-10 when adjacent lysine-9 is dimethylated (H3K9me2S10). Imaging and proteomic approaches show epidermal factor (EGF) stimulation results...
Abstract Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with immune infiltrate representing a key feature this process. Studies human T1D immunobiology have predominantly focused on circulating the blood, while mouse models suggest diabetogenic lymphocytes primarily reside pancreas-draining lymph nodes (pLN). A comprehensive study was conducted using pancreas draining lymphatic tissues, including pLN and mesenteric nodes, spleen from non-diabetic control, cell...
Abstract Despite extensive clinical evidence on the efficacy and safety of SARS-CoV-2 vaccines, there remains a paucity data their effectiveness in cancer patients who are actively receiving antineoplastic therapeutics. A recent study demonstrated only ~30% had positive serologic test following 2 doses FDA-authorized contrast to ~80% positivity rate healthy individuals, regardless age. Therefore, further investigation into novel approaches boost immune response vaccines is required. Our...
Abstract The fetal immune system undergoes many developmental milestones, with several cell subsets emerging during pregnancy. Recent evidence has shown that maternal infections pregnancy can influence offspring immunity in the long term. Moreover, are associated an increased risk for neurodevelopmental disorders offspring. Yet, our knowledge of dynamics brain throughout gestation and their response to inflammation remains limited. We sought characterize phenotype cells murine implantation...
Abstract Understanding the complexity of long-lived HIV reservoir during antiretroviral therapy (ART) remains a major impediment for cure research. To address this, we developed single-cell viral ASAPseq to precisely define unperturbed peripheral blood HIV-infected memory CD4+ T cell from treated people living with (ART-PLWH) via presence integrated accessible proviral DNA in concert epigenetic and surface protein profiling. We identified profound heterogeneity within between ART-PLWH,...