Monsef Benkirane
University of Montpellier
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Publication
Featured researches published by Monsef Benkirane.
Nature Medicine | 2016
Steven G. Deeks; Sharon R. Lewin; Anna Laura Ross; Jintanat Ananworanich; Monsef Benkirane; Paula M. Cannon; Nicolas Chomont; Jeffrey D. Lifson; Ying-Ru Lo; Daniel R. Kuritzkes; David J. Margolis; John W. Mellors; Deborah Persaud; Joseph D. Tucker; Françoise Barré-Sinoussi; Galit Alter; Judith D. Auerbach; Brigitte Autran; Dan H. Barouch; Georg M. N. Behrens; Marina Cavazzana; Zhiwei Chen; Éric A. Cohen; Giulio Maria Corbelli; Serge Eholié; Nir Eyal; Sarah Fidler; Laurindo Garcia; Cynthia I. Grossman; Gail E. Henderson
Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the groups strategy.
Molecular Cell | 2017
Mehdi Morchikh; Alexandra Cribier; Raoul Raffel; Sonia Amraoui; Julien Cau; Dany Severac; Emeric Dubois; Olivier Schwartz; Yamina Bennasser; Monsef Benkirane
The DNA-mediated innate immune response underpins anti-microbial defenses and certain autoimmune diseases. Here we used immunoprecipitation, mass spectrometry, and RNA sequencing to identify a ribonuclear complex built around HEXIM1 and the long non-coding RNA NEAT1 that we dubbed the HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex (HDP-RNP). The HDP-RNP contains DNA-PK subunits (DNAPKc, Ku70, and Ku80) and paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATRIN3). We show that binding of HEXIM1 to NEAT1 is required for its assembly. We further demonstrate that the HDP-RNP is required for the innate immune response to foreign DNA, through the cGAS-STING-IRF3 pathway. The HDP-RNP interacts with cGAS and its partner PQBP1, and their interaction is remodeled by foreign DNA. Remodeling leads to the release of paraspeckle proteins, recruitment of STING, and activation of DNAPKc and IRF3. Our study establishes the HDP-RNP as a key nuclear regulator of DNA-mediated activation of innate immune response through the cGAS-STING pathway.
Cell Reports | 2016
Mayte Coiras; Mercedes Bermejo; Benjamin Descours; Elena Mateos; Javier García-Pérez; María Rosa López-Huertas; Michael M. Lederman; Monsef Benkirane; José Alcamí
SUMMARY HIV-1 post-integration latency in CD4+ lymphocytes is responsible for viral persistence despite treatment, but mechanisms involved in the establishment of latent viral reservoirs are not fully understood. We determined that both interleukin 2 (IL-2) and IL-7 induced SAMHD1 phosphorylation in T592, abrogating its antiviral activity. However, IL-7 caused a much more profound stimulatory effect on HIV-1 reverse transcription and integration than IL-2 that required chemokine co-stimulation. Both cytokines barely induced transcription due to low NF-κB induction, favoring the establishment of latent reservoirs. Effect of IL-7 on SAMHD1 phosphorylation was confirmed in IL-7-treated patients (ACTG 5214 study). Dasatinib—a tyrosine-kinase inhibitor—blocked SAMHD1 phosphorylation induced by IL-2 and IL-7 and restored HIV-1 restriction. We propose that γc-cytokines play a major role in the reservoir establishment not only by driving homeostatic proliferation but also by increasing susceptibility of CD4+ lymphocytes to HIV-1 infection through SAMHD1 inactivation.
EBioMedicine | 2016
Christelle Brégnard; Jessica Guerra; Stephanie Dejardin; Frank Passalacqua; Monsef Benkirane; Nadine Laguette
Fanconi Anemia (FA) is a genetic disorder characterized by elevated cancer susceptibility and pro-inflammatory cytokine production. Using SLX4FANCP deficiency as a working model, we questioned the trigger for chronic inflammation in FA. We found that absence of SLX4 caused cytoplasmic DNA accumulation, including sequences deriving from active Long INterspersed Element-1 (LINE-1), triggering the cGAS-STING pathway to elicit interferon (IFN) expression. In agreement, absence of SLX4 leads to upregulated LINE-1 retrotransposition. Importantly, similar results were obtained with the FANCD2 upstream activator of SLX4. Furthermore, treatment of FA cells with the Tenofovir reverse transcriptase inhibitor (RTi), that prevents endogenous retrotransposition, decreased both accumulation of cytoplasmic DNA and pro-inflammatory signaling. Collectively, our data suggest a contribution of endogenous RT activities to the generation of immunogenic cytoplasmic nucleic acids responsible for inflammation in FA. The additional observation that RTi decreased pro-inflammatory cytokine production induced by DNA replication stress-inducing drugs further demonstrates the contribution of endogenous RTs to sustaining chronic inflammation. Altogether, our data open perspectives in the prevention of adverse effects of chronic inflammation in tumorigenesis.
Nature | 2018
Flavie Coquel; Maria-Joao Silva; Hervé Técher; Karina Zadorozhny; Sushma Sharma; Jadwiga Nieminuszczy; Clément Mettling; Elodie Dardillac; Antoine Barthe; Anne-Lyne Schmitz; Alexy Promonet; Alexandra Cribier; Amélie Sarrazin; Wojciech Niedzwiedz; Bernard S. Lopez; Vincenzo Costanzo; Lumir Krejci; Andrei Chabes; Monsef Benkirane; Yea-Lih Lin; Philippe Pasero
SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi–Goutières syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR–CHK1 checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS–STING pathway to induce expression of pro-inflammatory type I interferons. SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks.SAMHD1 has an essential role in the replication stress response and prevents inflammation by activating the MRE11 nuclease to degrade nascent DNA strands at stalled replication forks, thus enabling replication.
Nature | 2018
Benjamin Descours; Gael Petitjean; Monsef Benkirane
Archive | 2015
Nadine Laguette; Monsef Benkirane
Archive | 2009
Monsef Benkirane; Robinson Triboulet; Christine Chable-Bessia; Yamina Bennasser; Daniel Latreille; Oussama Meziane; Pascal Barbry; Bernard Mari; Jacques Reynes
Archive | 2009
Monsef Benkirane; Robinson Triboulet; Christine Chable-Bessia; Yamina Bennasser; Daniel Latreille; Oussama Meziane; Pascal Barbry; Bernard Mari; Jacques Reynes
Archive | 2008
Pascal Barbry; Monsef Benkirane; Yamina Bennasser; Christine Chable-Bessia; Daniel Latreille; Bernard Mari; Oussama Meziane; Jacques Reynes; Robinson Triboulet