Diagenode

HIV-2/SIV viral protein X counteracts HUSH repressor complex.


Ghina Chougui, Soundasse Munir-Matloob, Roy Matkovic, Michaël M Martin, Marina Morel, Hichem Lahouassa, Marjorie Leduc, Bertha Cecilia Ramirez, Lucie Etienne   and Florence Margottin-Goguet

To evade host immune defences, human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) have evolved auxiliary proteins that target cell restriction factors. Viral protein X (Vpx) from the HIV-2/SIVsmm lineage enhances viral infection by antagonizing SAMHD1 (refs ), but this antagonism is not sufficient to explain all Vpx phenotypes. Here, through a proteomic screen, we identified another Vpx target-HUSH (TASOR, MPP8 and periphilin)-a complex involved in position-effect variegation. HUSH downregulation by Vpx is observed in primary cells and HIV-2-infected cells. Vpx binds HUSH and induces its proteasomal degradation through the recruitment of the DCAF1 ubiquitin ligase adaptor, independently from SAMHD1 antagonism. As a consequence, Vpx is able to reactivate HIV latent proviruses, unlike Vpx mutants, which are unable to induce HUSH degradation. Although antagonism of human HUSH is not conserved among all lentiviral lineages including HIV-1, it is a feature of viral protein R (Vpr) from simian immunodeficiency viruses (SIVs) of African green monkeys and from the divergent SIV of l'Hoest's monkey, arguing in favour of an ancient lentiviral species-specific vpx/vpr gene function. Altogether, our results suggest the HUSH complex as a restriction factor, active in primary CD4 T cells and counteracted by Vpx, therefore providing a molecular link between intrinsic immunity and epigenetic control.

Tags
Antibody
HighCell ChIP kit

Share this article

Published
August, 2018

Source

Products used in this publication

  • Antibody ChIP-seq grade icon
    C15410069
    H3K27me3 polyclonal antibody
  • Antibody ChIP-seq grade icon
    C15410056
    H3K9me3 polyclonal antibody
  • Antibody ChIP icon
    C15310135
    H3pan polyclonal antibody
  • RFX5-polyclonal-antibody-diagenode
    C15410206
    Rabbit IgG
  • ChIP kit icon
    C01010062
    HighCell# ChIP kit protein A

         Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics