This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02376-07v1 82/6/2930    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Kramer, M. Articles by Adema, G. J. PubMed PubMed Citation Articles by Kramer, M. Articles by Adema, G. J.

Phagocytosis of Picornavirus-Infected Cells Induces an RNA-Dependent Antiviral State in Human Dendritic Cells

Matthijs Kramer,^1, Barbara M. Schulte,^2, Liza W. J. Toonen,¹ Paola M. Barral,³ Paul B. Fisher,³ Kjerstin H. W. Lanke,² Jochem M. D. Galama,² Frank J. M. van Kuppeveld,² and Gosse J. Adema^1*

Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences,¹ Department of Medical Microbiology, Nijmegen Centre for Molecular Life Sciences and Nijmegen University Centre for Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands,² Departments of Pathology, Neurosurgery and Urology, Columbia University, College of Physicians and Surgeons, New York, New York³

Received 2 November 2007/ Accepted 2 January 2008

Dendritic cells (DCs) play a central role in instructing antiviral immune responses. DCs, however, can become targeted by different viruses themselves. We recently demonstrated that human DCs can be productively infected with echoviruses (EVs), but not coxsackie B viruses (CVBs), both of which are RNA viruses belonging to the Enterovirus genus of the Picornaviridae family. We now show that phagocytosis of CVB-infected, type I interferon-deficient cells induces an antiviral state in human DCs. Uptake of infected cells increased the expression of the cytoplasmic RNA helicases retinoic acid-inducible gene I and melanoma differentiation-associated gene 5 as well as other interferon-stimulated genes and protected DCs against subsequent infection with EV9. These effects depended on recognition of viral RNA and could be mimicked by exposure to the synthetic double-stranded RNA analogue poly(I:C) but not other Toll-like receptor (TLR) ligands. Blocking endosomal acidification abrogated protection, suggesting a role for TLRs in the acquisition of an antiviral state in DCs. In conclusion, recognition of viral RNA rapidly induces an antiviral state in human DCs. This might provide a mechanism by which DCs protect themselves against viruses when attracted to an environment with ongoing infection.

Published ahead of print on 9 January 2008.

M.K. and B.M.S. contributed equally to this work.