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Plos Pathogens : Innate Sensing of Hiv-infected Cells, Volume 7

By Emerman, Michael

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Book Id: WPLBN0003962840
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Pathogens : Innate Sensing of Hiv-infected Cells, Volume 7  
Author: Emerman, Michael
Volume: Volume 7
Language: English
Subject: Journels, Science, Pathogens
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Pathogens
Historic
Publication Date:
Publisher: Plos

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Emerman, M. (n.d.). Plos Pathogens : Innate Sensing of Hiv-infected Cells, Volume 7. Retrieved from http://ebook.worldlibrary.net/


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Description : 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.

 

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