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)

1 U932 - Immunité et cancer
2 CDC - Compartimentation et dynamique cellulaires
3 IMRB - Institut Mondor de Recherche Biomédicale
4 Immunologie Clinique

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.

Domaines: Biochimie, Biologie Moléculaire

Xavier Lahaye, Takeshi Satoh, Matteo Gentili, Silvia Cerboni, Cécile Conrad, et al.. The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells.. Immunity, 2013, 39 (6), pp.1132-42. ⟨10.1016/j.immuni.2013.11.002⟩. ⟨inserm-00959028⟩