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Cell Host Microbe. 2012 Oct 18;12(4):558-70. doi: 10.1016/j.chom.2012.08.010.

Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity.

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. marlene.dreux@ens-lyon.fr

Abstract

Viral nucleic acids often trigger an innate immune response in infected cells. Many viruses, including hepatitis C virus (HCV), have evolved mechanisms to evade intracellular recognition. Nevertheless, HCV-permissive cells can trigger a viral RNA-, TLR7-, and cell-contact-dependent compensatory interferon response in nonpermissive plasmacytoid dendritic cells (pDCs). Here we report that these events are mediated by transfer of HCV-RNA-containing exosomes from infected cells to pDCs. The exosomal viral RNA transfer is dependent on the endosomal sorting complex required for transport (ESCRT) machinery and on Annexin A2, an RNA-binding protein involved in membrane vesicle trafficking, and is suppressed by exosome release inhibitors. Further, purified concentrated HCV-RNA-containing exosomes are sufficient to activate pDCs. Thus, vesicular sequestration and exosomal export of viral RNA may serve both as a viral strategy to evade pathogen sensing within infected cells and as a host strategy to induce an unopposed innate response in replication-nonpermissive bystander cells.

PMID:
23084922
PMCID:
PMC3479672
DOI:
10.1016/j.chom.2012.08.010
[Indexed for MEDLINE]
Free PMC Article

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