2. Academic Validation
  3. NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation

NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation

  • Cell. 2018 Oct 4;175(2):488-501.e22. doi: 10.1016/j.cell.2018.08.062.
Xavier Lahaye 1,  Matteo Gentili 1,  Aymeric Silvin 1,  Cécile Conrad 1,  Léa Picard 2,  Mabel Jouve 1,  Elina Zueva 1,  Mathieu Maurin 1,  Francesca Nadalin 1,  Gavin J Knott 3,  Baoyu Zhao 4,  Fenglei Du 4,  Marlène Rio 5,  Jeanne Amiel 5,  Archa H Fox 6,  Pingwei Li 4,  Lucie Etienne 7,  Charles S Bond 3,  Laurence Colleaux 5,  Nicolas Manel 8
Affiliations

Affiliations

  • 1 Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
  • 2 CIRI-International Center for Infectiology Research, Inserm U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, Univ Lyon, 69007 Lyon, France; LBBE-Laboratoire de Biométrie et Biologie Evolutive CNRS UMR 5558, Universite Lyon 1, Univ Lyon, 69622 Villeurbanne, France.
  • 3 School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia.
  • 4 Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
  • 5 INSERM UMR 1163, Paris-Descartes-Sorbonne Paris Cité University, Institut IMAGINE, Necker-Enfants Malades Hospital, 75015 Paris, France; Service de Génétique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
  • 6 School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia; School of Human Sciences, The University of Western Australia, Crawley, WA 6009, Australia; The Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA 6009, Australia.
  • 7 CIRI-International Center for Infectiology Research, Inserm U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, Univ Lyon, 69007 Lyon, France.
  • 8 Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. Electronic address: [email protected].
PMID: 30270045 DOI: 10.1016/j.cell.2018.08.062
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.

Keywords

HIV-1; HIV-2; NONO; STING; cGAS; capsid; dendritic cells; innate immune sensors; innate immunity; macrophages.

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