Innate sensing of HIV-infected cells
MetadataShow full item record
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.
Lepelley , A , Louis , S , Sourisseau , M , Law , H K W , Pothlichet , J , Schilte , C , Chaperot , L , Plumas , J , Randall , R E , Si-Tahar , M , Mammano , F , Albert , M L & Schwartz , O 2011 , ' Innate sensing of HIV-infected cells ' PLoS Pathogens , vol. 7 , no. 2 , e1001284 . DOI: 10.1371/journal.ppat.1001284
© 2011 Lepelley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.