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    HIV: Retrovirus, Infection and Latency

    Team leader : Florence Margottin-Goguet

    Our team’s work focuses on the molecular conflicts which exist between viruses and their cellular hosts. These include the hijacking of the cellular machinery from the virus’ point of view, and overcoming the infection from the cell’s point of view.

    Human Immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) are responsible for Acquired Immunodeficiency Syndrome (AIDS). Today, about 38 million people are living with HIV worldwide. HIV eradication faces a major obstacle that is viral persistence in reservoir cells despite treatment. HIV latency refers to silent viruses, which may remain competent for virus production if the treatment is interrupted. 

    HIV-1 and HIV-2 appeared in humans after cross-species transmission from non-human primate viruses (simian Immunodeficiency viruses or SIV). SIVcpz and SIVgor (infecting chimpanzee and gorilla, respectively) gave rise to HIV-1 on the one hand, SIVsmm (infecting sooty mangabey) to HIV-2 on the other hand. SIVsmm has also been transmitted to macaques (SIVmac). The different lineages share a similar “Gag-Pol-Env” organization but differ in their set of accessory proteins. For example, Vpx is found only in the HIV-2/SIVmac/SIVsmm and SIVrcm/mnd2 (infecting red-capped mangabey and mandrill) lineages. In contrast, all extant primate lentiviruses encode for Vpr, a paralog of Vpx, including SIVagm (infecting African green monkeys). These viral accessory proteins, which bear no structural or catalytic function, allow the virus to adapt to its host’s environment in order to ensure efficient replication and survival in the infected cells.

    In some circumstances, cross-species transmission is blocked by host defence proteins, the so-called “restriction factors”. Restriction factors (RFs) provide a first line of defence against the virus within the host cell. They are characterized by their cell-autonomous antiviral activity and their interaction with a viral component. RFs often show signs of positive selection (an excess rate of non-synonymous mutations (dN) compared to the rate of synonymous mutations (dS)) that may be witnessed by comparing protein-coding sequences of genes from different host species. Those marks result from continual host-virus competition along evolution. This molecular arms-race can also be highlighted by the existence of viral antagonists in the form of the aforementioned viral accessory proteins. The mechanism of action of these viral antagonists often relies on the hijacking of a specific ubiquitin ligase to target the RF for degradation. 

     

    Objectives

    The molecular battle at stake between the host cell and the virus is at the heart of the ongoing research of our team. Our general objectives are to better understand the role of viral auxiliary proteins and to identify and characterize host restrictions factors. 

    Our main lines of research are:

    • The search for host protein targets of the Vpr and Vpx proteins from HIV-1/HIV-2
    • The search of the genuine function of HIV-1 Vpr
    • The identification and study of host factors from the innate antiviral defense arsenal (restriction factors), which represent potential targets of our viral proteins.

    We expect our study to provide a better understanding of viral pathogenesis that might be taken into account in therapeutic strategies.

     

    Selection of some contributions of the team to the HIV field

     

    Group composition

    • MARGOTTIN-GOGUET Florence, team leader, Research director INSERM
      Orcid number: 0000-0002-3124-6690
      Researcher ID: F-9272-2013
      Web of Science: indicate for "author": "Margottin F or Margottin-Goguet F"
      Pubmed link :  http://www.ncbi.nlm.nih.gov/pubmed?term=Margottin-goguet F[Author] or Margottin F[Author]
    • MOREL Marina, engineering assistant, CNRS
    • MATKOVIC Roy, postdoc
    • VAUTHIER Virginie, postdoc
    • MARTIN Michael, PhD student
    • LASSERRE Angélique, PhD student
    • LARROUS Pauline, PhD student

     

    Selected publications

     

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