Laboratory of Molecular Virology

 Monsef BENKIRANE

 IGH - UMR 9002

 141, rue de la Cardonille, 34396 Montpellier

Phone: +33 4 34 35 99 96

Email:monsef.benkirane@igh.cnrs.fr

Website

The laboratory of molecular virology has a long-standing experience in the field of HIV gene expression, small non-coding RNA and viral restriction field. The Team has established important tools and strong collaborations (local, national and international) in these fields. Our major aim is to understand the complex interaction between HIV and its host with particular emphasis on viral persistence. During the last 10 years our laboratory made important contributions to the current understanding of how the viral transactivator Tat protein overcomes chromatin restriction and RNA polymerase II pausing at the viral LTR. We identified the cellular pathways involved in HIV transcriptional silencing and highlighted the important of chromatin repressors and RNAi in the establishment and the maintenance of viral persistence. More recently, we identified SAMHD1 as the HIV restriction factor operating in myeloid cells.

Our project aims at (i) increasing knowledge on the contribution of immune activation and inflammation to HIV persistence (ii) deciphering the cellular and molecular mechanisms of viral persistence (iii) translating this basic knowledge into novel targets to achieve a cure for HIV/AIDS.

Keywords: HIV, Persistence, transcription elongation, chromatin, restriction, miRNA

Main publications

• Laguette N, Rahm N, So., Delsuc , F., Telenti, A., and Benkirane, M bhian B, Chable-Bessia C, Munch J, Snoeck J, Sauter D, Switzer WM, Heneine W, Kirchhoff F., Delsuc , F., Telenti, A., and Benkirane, M: Evolutionary and Functional Analyses of the Interaction between the Myeloid Restriction Factor SAMHD1 and the Lentiviral Vpx Protein. Cell Host Microbe 2012. Feb 1. [Epub ahead of print].
• Laguette N, Benkirane M. How Samhd1 changes our view of viral restriction. Trends Immunol. 2012 Jan;33(1):26-33. Epub 2011 Dec 15.
• Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M: SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 2011, 474(7353):654-657.
• Bennasser, Y., Chable-Bessia, C., Triboulet, R., Gibbings, D., Gwizdek, C., Dargemont, C., Kremer, E.J., Voinnet, O., and Benkirane, M. (2011). Competition for XPO5 binding between Dicer mRNA, pre-miRNA and viral RNA regulates human Dicer levels. Nat Struct Mol Biol. Mar;18(3):323-7.
• He N, Chan CK, Sobhian B, Chou S, Xue Y, Liu M, Alber T, Benkirane M, Zhou Q: Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin. Proc Natl Acad Sci U S A 2011.
• Sobhian, B., Laguette, N., Yatim, A., Nakamura, M., Levy, Y., Kiernan, R., and Benkirane, M. (2010). HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. Mol Cell 38, 439-451.
• Triboulet, R., Mari, B., Lin, Y.L., Chable-Bessia, C., Bennasser, Y., Lebrigand, K., Cardinaud, B., Maurin, T., Barbry, P., Baillat, V., Reynes, J, Corbeau, P, Jeang, KT, and Benkirane, M. (2007). Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315, 1579-1582.
• du Chene I, Basyuk E, Lin YL, Triboulet R, Knezevich A, Chable-Bessia C, Mettling C, Baillat V, Reynes J, Corbeau P, Bertrand E, Marcello A, Emiliani S, Kiernan R, Benkirane M. (2007). Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. Embo J 26, 424-435.
• Linares, L.K., Kiernan, R., Triboulet, R., Chable-Bessia, C., Latreille, D., Cuvier, O., Lacroix, M., Le Cam, L., Coux, O., and Benkirane, M. (2007). Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2. Nat Cell Biol 9, 331-338.
• Bres V, Kiernan RE, Linares LK, Chable-Bessia C, Plechakova O, Treand C, Emiliani S, Peloponese JM, Jeang KT, Coux O, Scheffner M, Benkirane M. (2003). A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter. Nat Cell Biol 5, 754-761.