Innate sensing of HIV-infected cells

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. © 2011 lepelley et al.