title: The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells.
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.
authors.affiliation: Institut Curie, 12 rue Lhomond, 75005 Paris, France; INSERM U932, 12 rue Lhomond, 75005 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Lahaye
authors.affiliation: Institut Curie, 12 rue Lhomond, 75005 Paris, France; INSERM U932, 12 rue Lhomond, 75005 Paris, France.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Institut Curie, 12 rue Lhomond, 75005 Paris, France; INSERM U932, 12 rue Lhomond, 75005 Paris, France.
authors.forename: Matteo
authors.initials: M
authors.lastname: Gentili
authors.affiliation: Institut Curie, 12 rue Lhomond, 75005 Paris, France; INSERM U932, 12 rue Lhomond, 75005 Paris, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cerboni
authors.affiliation: Institut Curie, 12 rue Lhomond, 75005 Paris, France; INSERM U932, 12 rue Lhomond, 75005 Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Institut Curie, 12 rue Lhomond, 75005 Paris, France; CNRS UMR144, 12 rue Lhomond, 75005 Paris, France.
authors.forename: Ilse
authors.initials: I
authors.lastname: Hurbain
authors.affiliation: Institut Curie, 12 rue Lhomond, 75005 Paris, France; CNRS UMR144, 12 rue Lhomond, 75005 Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El Marjou
authors.affiliation: INSERM U955, Vaccine Research Institute, Université Paris Est Créteil, Faculté de Médecine, 94010 Créteil, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lacabaratz
authors.affiliation: 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.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lelièvre
authors.affiliation: Institut Curie, 12 rue Lhomond, 75005 Paris, France; INSERM U932, 12 rue Lhomond, 75005 Paris, France. Electronic address: nicolas.manel@curie.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Manel
mesh_terms: D002213:Capsid / Q000276:immunology*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015498:HIV-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D008954:Models, Biological; D009713:Nucleotidyltransferases / Q000378:metabolism*; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D018076:DNA, Complementary; D004279:DNA, Viral; D009713:Nucleotidyltransferases; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase