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Volume 8 Supplement 2

Frontiers of Retrovirology 2011

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Novel insights into innate sensing of HIV-infected cells

Our research is aimed at understanding the interplay between viruses and the immune system. We are analyzing how HIV infection triggers production of type-l interferon (IFN) and other cytokines in various cell types. Cell-free HIV-1 virions are considered to be poor stimulators of IFN production. We examined how HIV-infected cells are recognized by plasmacytoid dendritic cells (pDCs), by monocyte-derived DCs (MDDCs), 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 viral sensing. 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. We are also currently analyzing the role of SAMHD1, a recently identified anti-HIV restriction factor, in the activation of MDDCs by HIV. Altogether, our results indicate that detection of HIV-infected lymphocytes occurs at different levels, 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.

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This article is published under license to BioMed Central Ltd. 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 work is properly cited.

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Schwartz, O. Novel insights into innate sensing of HIV-infected cells. Retrovirology 8 (Suppl 2), O13 (2011).

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