Innate sensing of HIV-infected cells

Alice Lepelley, Stéphanie Louis, Marion Sourisseau, Ka Wai Helen Law, Julien Pothlichet, Clémentine Schilte, Laurence Chaperot, Joël Plumas, Richard E. Randall, Mustapha Si-Tahar, Fabrizio Mammano, Matthew L. Albert, Olivier Schwartz

Research output: Journal article publicationJournal articleAcademic researchpeer-review

160 Citations (Scopus)

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.
Original languageEnglish
Article numbere1001284
JournalPLoS Pathogens
Volume7
Issue number2
DOIs
Publication statusPublished - 1 Feb 2011
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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