A5071997592- RNA Research and Splicing
- HIV Research and Treatment
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Nanopore and Nanochannel Transport Studies
- HIV/AIDS drug development and treatment
- interferon and immune responses
- Biochemical and Molecular Research
- Mechanisms of cancer metastasis
- Mosquito-borne diseases and control
- Cancer Mechanisms and Therapy
- SARS-CoV-2 and COVID-19 Research
- Cytomegalovirus and herpesvirus research
- RNA regulation and disease
- MicroRNA in disease regulation
- Cancer, Stress, Anesthesia, and Immune Response
- Pharmacological Receptor Mechanisms and Effects
- Synthesis of Tetrazole Derivatives
- Neuropeptides and Animal Physiology
- Calcium signaling and nucleotide metabolism
- Influenza Virus Research Studies
- HIV/AIDS Research and Interventions
- Viral-associated cancers and disorders
- Viral Infections and Vectors
- Enzyme function and inhibition
Centre National de la Recherche Scientifique
2004-2024
Institut Cochin
2012-2024
Inserm
2012-2024
Université Paris Cité
2012-2024
Sorbonne Paris Cité
2012-2021
Délégation Paris 5
2012-2016
King's College London
2006-2009
King's College School
2008
Institut Pasteur
2002-2007
Guy's Hospital
2007
ABSTRACT Members of the APOBEC ( apo lipoprotein B mRNA- e diting enzyme c atalytic polypeptide 1-like) family cytidine deaminases inhibit host cell genome invasion by exogenous retroviruses and endogenous retrotransposons. Because these enzymes can edit DNA or RNA potentially mutate cellular targets, their activities are presumably regulated; for instance, APOBEC3G (A3G) recruitment into high-molecular-weight ribonucleoprotein (RNP) complexes has been shown to suppress its enzymatic...
The human cytidine deaminase APOBEC3G (A3G) is a potent inhibitor of retroviruses and transposable elements able to deaminate cytidines uridines in single-stranded DNA replication intermediates. A3G contains two canonical domains (CDAs), which only the C-terminal one known mediate deamination. By exploiting crystal structure related tetrameric APOBEC2 (A2) protein, we identified residues within that have potential oligomerization protein. Using yeast two-hybrid assays,...
Abstract The Human Silencing Hub (HUSH) complex constituted of TASOR, MPP8 and Periphilin recruits the histone methyl-transferase SETDB1 to spread H3K9me3 repressive marks across genes transgenes in an integration site-dependent manner. deposition these leads heterochromatin formation inhibits gene expression, but underlying mechanism is not fully understood. Here, we show that TASOR silencing or HIV-2 Vpx which induces degradation, increases accumulation transcripts derived from HIV-1 LTR...
Dengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue disease, major human health concern which no effective treatment available. DENV relies heavily on the host cellular machinery productive infection. Here, we show that scaffold protein RACK1, part of replication complex, mediates infection by binding to 40S ribosomal subunit. Mass spectrometry analysis RACK1 partners coupled an RNA interference screen-identified Vigilin and SERBP1 as host-dependency factors. Both are...
The human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3F (APOBEC3F [A3F]) and A3G proteins are effective inhibitors of infection by various retroelements share approximately 50% amino acid sequence identity. We therefore undertook comparative analyses the protein RNA compositions A3F- A3G-associated ribonucleoprotein complexes (RNPs). Like A3G, A3F is found associated with a complex array cytoplasmic RNPs can accumulate in RNA-rich microdomains known as mRNA processing...
Abstract Background Alternative splicing is a key step in Human Immunodeficiency Virus type 1 (HIV-1) replication that tightly regulated both temporally and spatially. More than 50 different transcripts can be generated from single HIV-1 unspliced pre-messenger RNA (pre-mRNA) balanced proportion of spliced critical for the production infectious virions. Understanding mechanisms involved regulation viral therefore potential therapeutic interest. However, monitoring alternative events at...
Tripartite motif (TRIM)5 alpha has recently been identified as a host restriction factor that the ability to block infection by certain retroviruses in species-dependent manner. One interesting feature of this protein is it localized distinct cytoplasmic clusters designated bodies. The potential role these bodies TRIM5 function remains be defined. By using fluorescent fusion proteins and live cell microscopy, we studied localization dynamics This analysis reveals are highly mobile,...
BST2 (bone marrow stromal antigen 2)/tetherin is a restriction factor of enveloped viruses, which blocks the release viral particles. HIV-1 encodes proteins that antagonize this innate barrier, including accessory protein Vpu. Here, we investigate whether autophagy pathway and/or ATG are hijacked by Vpu to circumvent release. We report and present in LC3-positive compartments. found selectively interacts with ATG8 ortholog LC3C through L63VEM66 sequence. This sequence required for...
Abstract Background The recent discovery of the role m 6 A methylation in regulation HIV-1 replication unveiled a novel layer for HIV gene expression. This epitranscriptomic modification RNAs is under dynamic control specific writers and erasers. In addition, cytoplasmic readers mark are recruited to modified viral regulate replication. Yet, little known about effects on biogenesis RNAs. Results We showed that METTL3/14 methyltransferase complex YTHDF2 reader down regulates abundance...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused current disease (COVID) pandemic. Viral infection relies on viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of replication. To identify chemical tools further study these functional interfaces, 139,146 compounds from different libraries were screened through an S/ACE2
Bone marrow stromal antigen 2 (BST2)/tetherin is a restriction factor that reduces HIV-1 dissemination by tethering virus at the cell surface. BST2 also acts as sensor of budding, establishing cellular antiviral state. The Vpu protein antagonizes functions via multiple mechanisms, including subversion an LC3C-associated pathway, key intrinsic antimicrobial mechanism. Here, we describe first step this viral-induced process. This process initiated plasma membrane through recognition and...
UMP‐CMP kinase catalyses an important step in the phosphorylation of UTP, CTP and dCTP. It is also involved necessary by cellular kinases nucleoside analogs used antiviral therapies. The reactivity human towards natural substrates nucleotide was reexamined. expression recombinant enzyme conditions for stability were improved. Substrate inhibition observed UMP CMP at concentrations higher than 0.2 m , but not dCMP. analog l ‐3TCMP found to be efficient substrate phosphorylated into ‐3TCDP...
Argonaute (Ago) proteins associate with microRNAs (miRNAs) to form the core of RNA-induced silencing complex (RISC) that mediates post-transcriptional gene target mRNAs. As key players in anti-viral defense, Ago are thought have ability interact human immunodeficiency virus type 1 (HIV-1) RNA. However, role this interaction regulating HIV-1 replication has been debated. Here, we used high throughput sequencing RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) explore between Ago2...
Antiviral nucleoside analog therapies rely on their incorporation by viral DNA polymerases/reverse transcriptase leading to chain termination. The analogs (3′-deoxy-3′-azidothymidine (AZT), 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T), and other dideoxynucleosides) are sequentially converted into triphosphate cellular kinases of the salvage pathway often poor substrates these enzymes. Nucleoside diphosphate (NDP) kinase phosphorylates derivatives with an efficiency some 104 lower than for...
Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested vitro RNA polymerases of HCV, phage T7, HIV-1 reverse transcriptase. Modified nucleotides with 2′-deoxy, 3′-deoxy, 2′,3′-dideoxy, 2′,3′-dideoxy-2′,3′-dehydro, 2′,3′-epoxy-ribose inhibited HCV enzyme not two polymerases. They also analyzed as substrates for...
Methylanthraniloyl derivatives of ATP and CDP were used in vitro as fluorescent probes for the donor‐binding acceptor‐binding sites human UMP‐CMP kinase, a nucleoside salvage pathway kinase. Like all NMP kinases, kinase binds phosphodonor, usually ATP, at different binding sites. The reaction results from an in‐line phosphotransfer donor to acceptor. probe site was displaced by bisubstrate analogs Ap5X series (where X = U, dT, A, G), indicating broad specificity acceptor site. Both CMP dCMP...
Upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients critical disease 2019 (COVID-19) present life-threatening distress, pulmonary damage, and cytokine storm. One unexplored component in COVID-19 is the neuropeptide calcitonin gene-related peptide (CGRP), which highly abundant airways could converge multiple aspects of COVID-19-related pathophysiology. Whether CGRP affects SARS-CoV-2 directly remains elusive. We show that patients, increased both plasma...
In evolution strategies aimed at isolating molecules with new functions, screening for the desired phenotype is generally performed in vitro or bacteria. When final goal of strategy modification human cell, mutants selected these preliminary screenings may fail to confer phenotype, due complex networks that regulate gene expression higher eukaryotes. We developed a system where, by mimicking successive infection cycles HIV-1 derived vectors containing target their genome, libraries are...