The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells.

Xavier Lahaye; Takeshi Satoh; Matteo Gentili; Silvia Cerboni; Cécile Conrad; Ilse Hurbain; Ahmed El Marjou; Christine Lacabaratz; Jean-Daniel Lelièvre; Nicolas Manel

doi:10.1016/j.immuni.2013.11.002

The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells.

Xavier Lahaye ¹ Takeshi Satoh ¹ Matteo Gentili ¹ Silvia Cerboni ¹ Cécile Conrad ¹ Ilse Hurbain ^{1, 2} Ahmed El Marjou ^{1, 2} Christine Lacabaratz ³ Jean-Daniel Lelièvre ^{3, 4} Nicolas Manel ^{1, *}

* Auteur correspondant

1 U932 - Immunité et cancer

2 CDC - Compartimentation et dynamique cellulaires

3 IMRB - Institut Mondor de Recherche Biomédicale

4 Immunologie Clinique

Abstract : HIV-2 is less pathogenic for humans than HIV-1 and might provide partial cross-protection from HIV-1-induced pathology. Although both viruses replicate in the T cells of infected patients, only HIV-2 replicates efficiently in dendritic cells (DCs) and activates innate immune pathways. How HIV is sensed in DC is unknown. Capsid-mutated HIV-2 revealed that sensing by the host requires viral cDNA synthesis, but not nuclear entry or genome integration. The HIV-1 capsid prevented viral cDNA sensing up to integration, allowing the virus to escape innate recognition. In contrast, DCs sensed capsid-mutated HIV-1 and enhanced stimulation of T cells in the absence of productive infection. Finally, we found that DC sensing of HIV-1 and HIV-2 required the DNA sensor cGAS. Thus, the HIV capsid is a determinant of innate sensing of the viral cDNA by cGAS in dendritic cells. This pathway might potentially be harnessed to develop effective vaccines against HIV-1.

Type de document :

Article dans une revue

Immunity, Elsevier, 2013, 39 (6), pp.1132-42. 〈10.1016/j.immuni.2013.11.002〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire

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The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells.

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The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells.

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623

741

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