A5017267110- HIV Research and Treatment
- RNA Research and Splicing
- HIV/AIDS drug development and treatment
- Hepatitis B Virus Studies
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Liver physiology and pathology
- interferon and immune responses
- HIV-related health complications and treatments
- Pancreatic and Hepatic Oncology Research
- HIV/AIDS Research and Interventions
- Protein Degradation and Inhibitors
- RNA regulation and disease
- Liver Disease Diagnosis and Treatment
- Mosquito-borne diseases and control
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Viral Infections and Outbreaks Research
- Cancer therapeutics and mechanisms
- RNA and protein synthesis mechanisms
- Berberine and alkaloids research
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- Viral Infections and Vectors
- Cytomegalovirus and herpesvirus research
Erasmus MC
2019-2025
Erasmus University Rotterdam
2022-2024
Jewish General Hospital
2015-2020
McGill University
2015-2019
Reliance Industries (India)
2008
The molecular events that drive hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose use human liver organoids as platform for modeling HBV infection related tumorigenesis. We first describe ex vivo HBV-infection derived from healthy donor after challenge with recombinant or HBV-infected patient serum. produced covalently closed circular DNA (cccDNA) early antigen (HBeAg),...
The duality of liquid-liquid phase separation (LLPS) cellular components into membraneless organelles defines the nucleation both normal and disease processes including stress granule (SG) assembly. From mounting evidence LLPS utility by viruses, we discover that HIV-1 nucleocapsid (NC) protein condenses zinc-finger (ZnF)-dependent LLPSs are dynamically influenced cytosolic factors. ZnF-dependent Zinc (Zn2+)-chelation-sensitive NC-LLPS formed in live cells. NC-Zn2+ ejection reverses blockade...
An innovative approach to eliminate HIV-1-infected cells emerging out of latency, the major hurdle HIV-1 cure, is pharmacologically reactivate viral expression and concomitantly trigger intracellular pro-apoptotic pathways in order selectively induce cell death (ICD) infected cells, without reliance on extracellular immune system. In this work, we demonstrate effect DDX3 inhibitors inducing latent lines, primary CD4+ T from cART-suppressed people living with (PLWHIV). We used single-cell...
Unspliced, genomic HIV-1 RNA (vRNA) is a component of several ribonucleoprotein complexes (RNP) during the viral replication cycle. In earlier work, we demonstrated that host upframeshift protein 1 (UPF1), key factor in nonsense-mediated mRNA decay (NMD), colocalized and associated to structural Gag egress. this demonstrate new function for UPF1 regulation vRNA nuclear export. OPEN ACCESS Biomolecules 2015, 5 2809 We establish nucleocytoplasmic shuttling required exists two essential RNPs...
The ability of human immunodeficiency virus type 1 (HIV-1) to form a stable viral reservoir is the major obstacle an HIV-1 cure and post-transcriptional events contribute maintenance latency. RNA surveillance proteins such as UPF1, UPF2 SMG6 affect stability metabolism. In our previous work, we demonstrated that UPF1 stabilises genomic (vRNA) enhances its translatability in cytoplasm. Thus, this work evaluated influence on vRNA expression and, consequence, reactivation cells lymphoid...
The human immunodeficiency virus type 1 (HIV-1) genomic RNA (vRNA) has two major fates during viral replication: to serve as the template for structural and enzymatic proteins, or be encapsidated packaged into assembling virions vRNA in budding viruses. dynamic balance between translation encapsidation is mediated by numerous host including Staufen1. During HIV-1 infection, recruits Staufen1 assemble a distinct ribonucleoprotein complex promoting assembly. also rescues gene expression...
The nucleocapsid (NC) is an N-terminal protein derived from the HIV-1 Gag precursor polyprotein, pr55Gag NC possesses key functions at several pivotal stages of viral replication. For example, interaction between and host double-stranded RNA-binding Staufen1 was shown to regulate steps in replication cycle, such as multimerization genomic RNA encapsidation. In this work, we observed that overexpression leads induction stress granule (SG) assembly. NC-mediated SG assembly unique it resistant...
Mammalian cells harbour RNA quality control and degradative machineries such as nonsense-mediated mRNA decay that target cellular mRNAs for clearance from the cell to avoid aberrant gene expression. The role of host pathways in macrophages context human immunodeficiency virus type 1 (HIV-1) infection is yet be elucidated. Macrophages are directly infected by HIV-1, mediate dissemination contribute chronic activation inflammatory response observed individuals. Therefore, we characterized...
Introduction Bryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In research, it shown anti-HIV effects during acute infection reactivation latent in chronic infection. As effective CD8+ T cell responses are essential eliminating reactivated virus achieving cure, is important to investigate how bryostatin-1 affects HIV-specific cells. cells often become exhausted, showing reduced proliferative potential impaired cytokine production,...
Abstract The molecular events that drive Hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose use human liver organoids as platform for modeling HBV infection related tumorigenesis. We first describe ex vivo HBV-infection derived from healthy donor after challenge with recombinant or HBV-infected patient serum. infected produced cccDNA, expressed intracellular RNA proteins,...
Reactivation of the latent HIV-1 reservoir is a first step toward triggering decay. Here, we investigated impact BAF complex inhibitor pyrimethamine on people living with (PLWH). Twenty-eight PLWH suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) RNA at days 0 and 14. We observed rapid, modest, significant increase response...
Abstract Background Strategies toward HIV-1 cure aim to clear, inactivate, reduce, or immunologically control the virus from a pool of latently infected cells such that combination antiretroviral therapy (cART) can be safely interrupted. In order assess impact any putative curative interventions on size and inducibility latent reservoir, robust scalable assays are needed precisely quantify frequency containing inducible HIV-1. Methods We developed S pecific Qu antification Inducible HIV −1...
Abstract A major pharmacological strategy toward HIV cure aims to reverse latency in infected cells as a first step leading their elimination. While the unbiased identification of molecular targets physically associated with latent HIV-1 provirus would be highly valuable unravel determinants transcriptional repression and reversal, due technical limitations, this has been challenging. Here we use dCas9 targeted chromatin histone enrichment coupled mass spectrometry (Catchet-MS) probe...
Substantial efforts to eliminate or reduce latent HIV-1 reservoirs are underway in clinical trials and have created a critical demand for sensitive, accurate, reproducible tools evaluate the efficacy of these strategies. Alternative reservoir quantification assays been developed circumvent limitations quantitative viral outgrowth assay. One such assay is tat/rev induced limiting dilution (TILDA), which measures frequency CD4+ T cells harboring inducible provirus. We modified...
A major unmet clinical need is a therapeutic capable of removing hepatitis B virus (HBV) genome from the liver infected individuals to reduce their risk developing cancer. strategy deliver such therapy could utilize ability target and promote apoptosis hepatocytes. Presently there no clinically relevant that has been shown effectively remove persistent episomal covalently closed circular HBV DNA (cccDNA) nucleus We used linearized single length various genotypes establish cccDNA-like...
Summary Strategies toward HIV-1 cure aim to clear, inactivate, reduce or immunologically control the virus from a pool of latently infected cells such that combination antiretroviral therapy (cART) can be safely interrupted. In order assess impact any putative curative interventions on size and inducibility latent reservoir, robust scalable assays are needed precisely quantify frequency containing inducible replication competent HIV-1. Here, we present Specific Quantification Inducible by...
Abstract Analytical treatment interruption (ATI) studies are increasingly being performed to evaluate the efficacy of putative strategies towards HIV-1 reservoir elimination or antiretroviral therapy (ART)-free viral control. A limited number have evaluated impact ATI on in individuals suppressive ART. Available data suggests that ATIs transient reservoir, mostly measured by levels total integrated DNA, peripheral blood cells prior and shortly after ART-mediated re-suppression. The long-term...
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