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

M Dreux, U Garaigorta, B Boyd, E Décembre, J Chung… - Cell host & …, 2012 - cell.com
M Dreux, U Garaigorta, B Boyd, E Décembre, J Chung, C Whitten-Bauer, S Wieland…
Cell host & microbe, 2012cell.com
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 …
Summary
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.
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