Biomedical research institute
     
    You are here: Home / Departments / Infection, Immunity and Inflammation / Team C. Pique, F. Margottin-Goguet

    Team: Retrovirus, Quiescence and Proliferation

    •  

    Team Leaders


    THE TEAM IN BRIEF... Human pathogenic retroviruses arise from two genera, the deltaretrovirus genus with HTLV-1, and the lentivirus genus with HIV-1 and HIV-2. HTLV-1 is responsible of T-cell leukemia and lymphoma, and of a demyelinating disease called HTLV-I associated myelopathy/Tropical spastic paraparesis (HAM/TSP) and HIV is responsible of AIDS.

     

     

    Objectives


    HTLV-1 and HIV share important common points: they are RNA viruses and, as an obligate step in their life cycle, they reverse transcribe their RNA genome into a cDNA copy that reaches the host chromatin and integrates into the host genome. The basic cycle of both viruses, from the attachment to the production of viral particles, is governed by the activity of the products of the Gag, Env and Pol genes and by regulating proteins, Tat and Rev in the case of HIV, Tax and Rex in the case of HTLV. Besides these essential proteins, both viruses express a set of so-called auxiliary proteins. In the case of HIV, the auxiliary proteins are experts in manipulating the cellular environment to allow optimal viral replication. In the case of HTLV-1, those proteins have been implicated in the regulation of viral transcription and latency as well as in the modulation of T-cell proliferation.
    On the cell side, CD4+ T lymphocytes are major cellular targets of both HIV and HTLV, but here the similarities stop. First, the outcomes of the infections are very different: while T cells infected by HTLV actively divide and become immortalized and for a fraction of them, transformed, T cells infected by HIV quickly die following the massive production of viral particles, which are ready to infect new cells. Second, while HTLV is believed to only infect dividing cells, mainly activated CD4+ T lymphocytes, HIV distinguishes himself by its capacity to also infect quiescent cells of the myeloid lineage such as macrophages. These myeloid cells survive HIV viral infection and constitute viral reservoirs of latent viruses.

    Altogether, comparing the molecular strategies developed by HTLV-1 and HIV to replicate in cells appears as a promising strategy to understand how viruses deal with the cellular environment. With this in mind, the general objective of our team is to explore the interplay between HTLV-1 and HIV and the cycling status of the host cell.

     

     

    Main publications

     

    Pène S, Waast L, Bonnet A, Bénit L, Pique C.A Non-SUMOylated Tax Protein Is Still Functional for NF-κB Pathway Activation. J Virol. 2014 Sep 15;88(18):10655-61.

    Blondot ML, Dragin L, Lahouassa H, Margottin-Goguet F. How SLX4 cuts through the mystery of HIV-1 Vpr-mediated cell cycle arrest. Retrovirology. 2014 Dec 11;11(1):117.

    Dragin L, Nguyen LA, Lahouassa H, Sourisce A, Kim B, Ramirez BC, Margottin-Goguet F. Interferon block to HIV-1 transduction in macrophages despite SAMHD1 degradation and high deoxynucleoside triphosphates supply. Retrovirology. 2013 Mar 11;10:30.

    Bonnet A, Randrianarison-Huetz V, Nzounza P, Nedelec M, Chazal M, Waast L, Pene S, Bazarbachi A, Mahieux R, Bénit L, Pique C. Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation. Retrovirology. 2012 Sep 25;9:77.

    Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, Bloch N, Maudet C, Bertrand M, Gramberg T, Pancino G, Priet S, Canard B, Laguette N, Benkirane M, Transy C, Landau NR, Kim B, Margottin-Goguet F.SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol. 2012 Feb 12;13(3):223-8.

    Nzounza P, Chazal M, Guedj C, Schmitt A, Massé JM, Randriamampita C, Pique C, Ramirez BC.The scaffolding protein Dlg1 is a negative regulator of cell-free virus infectivity but not of cell-to-cell HIV-1 transmission in T cells. PLoS One. 2012;7(1):e30130.

     

    Funding

     

    logo