NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation. | Academic Article individual record
abstract

Detection of viruses by innate immune sensors induces protective antiviral immunity. The viral DNA sensor cyclic GMP-AMP synthase (cGAS) is necessary for detection of HIV by human dendritic cells and macrophages. However, synthesis of HIV DNA during infection is not sufficient for immune activation. The capsid protein, which associates with viral DNA, has a pivotal role in enabling cGAS-mediated immune activation. We now find that NONO is an essential sensor of the HIV capsid in the nucleus. NONO protein directly binds capsid with higher affinity for weakly pathogenic HIV-2 than highly pathogenic HIV-1. Upon infection, NONO is essential for cGAS activation by HIV and cGAS association with HIV DNA in the nucleus. NONO recognizes a conserved region in HIV capsid with limited tolerance for escape mutations. Detection of nuclear viral capsid by NONO to promote DNA sensing by cGAS reveals an innate strategy to achieve distinction of viruses from self in the nucleus.

authors
author list (cited authors)
Lahaye, X., Gentili, M., Silvin, A., Conrad, C., Picard, L., Jouve, M., ... Manel, N.
publication date
2018
publisher
Elsevier bv Publisher
published in
CELL Journal
keywords
  • Capsid Proteins
  • Dendritic Cells
  • Capsid
  • HIV-1
  • Immunity, Innate
  • DNA, Viral
  • Host-Pathogen Interactions
  • Nono
  • Nucleotidyltransferases
  • Innate Immune Sensors
  • Cgas
  • Macrophages
  • Innate Immunity
  • Signal Transduction
  • Nuclear Matrix-associated Proteins
  • HIV-2
  • Octamer Transcription Factors
  • HIV Infections
  • Membrane Proteins
  • RNA-Binding Proteins
  • Sting
  • Cell Nucleus
  • Humans
altmetric score

62.8

citation count

46