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Immunity. 2013 Dec 12;39(6):1132-42. doi: 10.1016/j.immuni.2013.11.002. Epub 2013 Nov 21.

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

Author information

1
Institut Curie, 12 rue Lhomond, 75005 Paris, France; INSERM U932, 12 rue Lhomond, 75005 Paris, France.
2
Institut Curie, 12 rue Lhomond, 75005 Paris, France; CNRS UMR144, 12 rue Lhomond, 75005 Paris, France.
3
INSERM U955, Vaccine Research Institute, Université Paris Est Créteil, Faculté de Médecine, 94010 Créteil, France.
4
INSERM U955, Vaccine Research Institute, Université Paris Est Créteil, Faculté de Médecine, 94010 Créteil, France; AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie clinique, 94010 Créteil, France.
5
Institut Curie, 12 rue Lhomond, 75005 Paris, France; INSERM U932, 12 rue Lhomond, 75005 Paris, France. Electronic address: nicolas.manel@curie.fr.

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.

PMID:
24269171
DOI:
10.1016/j.immuni.2013.11.002
[Indexed for MEDLINE]
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