Innate Sensing of HIV-Infected Cells

• DOI: 10.1371/journal.ppat.1001284
• Publication Date: 2011-02-17T19:48:14Z
• Authors: Alice Lepelley; Stéphanie Louis; Marion Sourisseau; Helen K. W. Law; Julien Pothlichet; Clémentine Schilte; Laurence Chaperot; Joël Plumas; Richard E. Randall; Mustapha Si-Tahar; Fabrizio Mammano; Matthew L. Albert; Olivier Schwartz
• Keywords: TLR7; IRF3; Cell fusion

Cell-free HIV-1 virions are poor stimulators of type I interferon (IFN) production. We examined here how HIV-infected cells recognized by plasmacytoid dendritic (pDCs) and other cells. show that infected lymphocytes more potent inducers IFN than virions. There target cell-type differences in the recognition lymphocytes. In primary pDCs pDC-like cells, occurs large part through TLR7, as demonstrated use inhibitors TLR7 silencing. Donor expressing replication-defective viruses, carrying mutated reverse transcriptase, integrase or nucleocapsid proteins induced production potently wild-type virus. contrast, Env-deleted fusion defective mutants were less efficient, suggesting addition to cytoplasmic cellular sensors may also mediate sensing Furthermore, a model TLR7-negative we demonstrate IRF3 pathway, process requiring access incoming viral material cytoplasm, allows Therefore, detection both endosomal pathways. Characterization mechanisms innate better understanding pathogenic exacerbated immunologic events associated with HIV infection.