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

Xavier Lahaye, Matteo Gentili, Aymeric Silvin, Cécile Conrad, Léa Picard, Mabel Jouve, Elina Zueva, Mathieu Maurin, Francesca Nadalin, Gavin J. Knott, Baoyu Zhao, Fenglei Du, Marlène Rio, Jeanne Amiel, Archa H. Fox, Pingwei Li, Lucie Etienne, Charles S. Bond, Laurence Colleaux, Nicolas Manel

Research output: Contribution to journalArticle

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. The cellular factor NONO activates cGAS-mediated innate immune defenses against HIV-2 infection via viral capsid binding.

LanguageEnglish
Pages488-501.e22
JournalCell
Volume175
Issue number2
DOIs
StatePublished - 4 Oct 2018

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GMP synthase (glutamine-hydrolyzing)
Capsid
Chemical activation
HIV
HIV-2
Viral DNA
Viruses
DNA
Sensors
Macrophages
Capsid Proteins
Infection
Dendritic Cells
HIV Infections
Antiviral Agents
cyclic guanosine monophosphate-adenosine monophosphate
HIV-1
Immunity
Association reactions

Cite this

Lahaye, X., Gentili, M., Silvin, A., Conrad, C., Picard, L., Jouve, M., ... Manel, N. (2018). NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation. Cell, 175(2), 488-501.e22. DOI: 10.1016/j.cell.2018.08.062
Lahaye, Xavier ; Gentili, Matteo ; Silvin, Aymeric ; Conrad, Cécile ; Picard, Léa ; Jouve, Mabel ; Zueva, Elina ; Maurin, Mathieu ; Nadalin, Francesca ; Knott, Gavin J. ; Zhao, Baoyu ; Du, Fenglei ; Rio, Marlène ; Amiel, Jeanne ; Fox, Archa H. ; Li, Pingwei ; Etienne, Lucie ; Bond, Charles S. ; Colleaux, Laurence ; Manel, Nicolas. / NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation. In: Cell. 2018 ; Vol. 175, No. 2. pp. 488-501.e22
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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. The cellular factor NONO activates cGAS-mediated innate immune defenses against HIV-2 infection via viral capsid binding.",
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Lahaye, X, Gentili, M, Silvin, A, Conrad, C, Picard, L, Jouve, M, Zueva, E, Maurin, M, Nadalin, F, Knott, GJ, Zhao, B, Du, F, Rio, M, Amiel, J, Fox, AH, Li, P, Etienne, L, Bond, CS, Colleaux, L & Manel, N 2018, 'NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation' Cell, vol. 175, no. 2, pp. 488-501.e22. DOI: 10.1016/j.cell.2018.08.062

NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation. / Lahaye, Xavier; Gentili, Matteo; Silvin, Aymeric; Conrad, Cécile; Picard, Léa; Jouve, Mabel; Zueva, Elina; Maurin, Mathieu; Nadalin, Francesca; Knott, Gavin J.; Zhao, Baoyu; Du, Fenglei; Rio, Marlène; Amiel, Jeanne; Fox, Archa H.; Li, Pingwei; Etienne, Lucie; Bond, Charles S.; Colleaux, Laurence; Manel, Nicolas.

In: Cell, Vol. 175, No. 2, 04.10.2018, p. 488-501.e22.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Lahaye,Xavier

AU - Gentili,Matteo

AU - Silvin,Aymeric

AU - Conrad,Cécile

AU - Picard,Léa

AU - Jouve,Mabel

AU - Zueva,Elina

AU - Maurin,Mathieu

AU - Nadalin,Francesca

AU - Knott,Gavin J.

AU - Zhao,Baoyu

AU - Du,Fenglei

AU - Rio,Marlène

AU - Amiel,Jeanne

AU - Fox,Archa H.

AU - Li,Pingwei

AU - Etienne,Lucie

AU - Bond,Charles S.

AU - Colleaux,Laurence

AU - Manel,Nicolas

PY - 2018/10/4

Y1 - 2018/10/4

N2 - 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. The cellular factor NONO activates cGAS-mediated innate immune defenses against HIV-2 infection via viral capsid binding.

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KW - cGAS

KW - dendritic cells

KW - HIV-1

KW - HIV-2

KW - innate immune sensors

KW - innate immunity

KW - macrophages

KW - NONO

KW - STING

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Lahaye X, Gentili M, Silvin A, Conrad C, Picard L, Jouve M et al. NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation. Cell. 2018 Oct 4;175(2):488-501.e22. Available from, DOI: 10.1016/j.cell.2018.08.062