Skip to Main content Skip to Navigation
Journal articles

Innate sensing of HIV-infected cells.

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [80 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-00590930
Contributor : Mireille Gau <>
Submitted on : Friday, May 6, 2011 - 3:21:10 PM
Last modification on : Tuesday, October 20, 2020 - 1:04:02 PM
Long-term archiving on: : Sunday, August 7, 2011 - 2:35:54 AM

File

journal.ppat.1001284.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

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

Share

Metrics

Record views

885

Files downloads

568