Innate sensing of HIV-infected cells

Alice Lepelley, Stephanie Louis, Marion Sourisseau, Helen K. W. Law, Julien Pothlichet, Clementine Schilte, Laurence Chaperot, Joel Plumas, Richard Edward Randall, Mustapha Si-Tahar, Fabrizio Mammano, Matthew L. Albert, Olivier Schwartz

Research output: Contribution to journalArticlepeer-review

169 Citations (Scopus)
2 Downloads (Pure)

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
Number of pages15
JournalPLoS Pathogens
Volume7
Issue number2
DOIs
Publication statusPublished - Feb 2011

Keywords

  • Human-immunodeficiency-virus
  • Plasmacytoid dendritic cells
  • CD4(+) T-cells
  • I interferon-production
  • RIG-I
  • Antiviral responses
  • Alpha-interferon
  • IFN-alpha
  • Viral-infection
  • Adapter protein

Fingerprint

Dive into the research topics of 'Innate sensing of HIV-infected cells'. Together they form a unique fingerprint.

Cite this