Innate sensing of HIV-infected cells.

Alice Lepelley (1) , Stéphanie Louis (1) , Marion Sourisseau (1) , Helen K W Law (2) , Julien Pothlichet (3) , Clémentine Schilte (4) , Laurence Chaperot (5) , Joël Plumas (5) , Richard E Randall (6) , Mustapha Si-Tahar (3) , Fabrizio Mammano (1) , Matthew L Albert (4) , Olivier Schwartz (1)

1 Virus et Immunité
2 CIH - Centre d'immunologie humaine
3 Défense innée et inflammation
4 Immunobiologie des Cellules Dendritiques
5 UJF - Université Joseph Fourier - Grenoble 1
6 University of St Andrews [Scotland]

Cell-free HIV-1 virions are poor stimulators of type I interferon (IFN) production. We examined here how HIV-infected cells are recognized by plasmacytoid dendritic cells (pDCs) and by other cells. We show that infected lymphocytes are more potent inducers of IFN than virions. There are target cell-type differences in the recognition of infected lymphocytes. In primary pDCs and pDC-like cells, recognition occurs in large part through TLR7, as demonstrated by the use of inhibitors and by TLR7 silencing. Donor cells expressing replication-defective viruses, carrying mutated reverse transcriptase, integrase or nucleocapsid proteins induced IFN production by target cells as potently as wild-type virus. In contrast, Env-deleted or fusion defective HIV-1 mutants were less efficient, suggesting that in addition to TLR7, cytoplasmic cellular sensors may also mediate sensing of infected cells. Furthermore, in a model of TLR7-negative cells, we demonstrate that the IRF3 pathway, through a process requiring access of incoming viral material to the cytoplasm, allows sensing of HIV-infected lymphocytes. Therefore, detection of HIV-infected lymphocytes occurs through both endosomal and cytoplasmic pathways. Characterization of the mechanisms of innate recognition of HIV-infected cells allows a better understanding of the pathogenic and exacerbated immunologic events associated with HIV infection.

Domaines: Microbiologie et Parasitologie

Alice Lepelley, Stéphanie Louis, Marion Sourisseau, Helen K W Law, Julien Pothlichet, et al.. Innate sensing of HIV-infected cells.. PLoS Pathogens, 2011, 7 (2), pp.e1001284. ⟨10.1371/journal.ppat.1001284⟩. ⟨pasteur-00590930⟩