Recognition of single-stranded RNA viruses by Toll-like receptor 7
- Jennifer M. Lund*,†,
- Lena Alexopoulou*,†,‡,
- Ayuko Sato§,
- Margaret Karow¶,
- Niels C. Adams¶,
- Nicholas W. Gale¶,
- Akiko Iwasaki*,§,∥,**, and
- Richard A. Flavell*,∥,††
- *Section of Immunobiology, §Department of Epidemiology and Public Health, ††Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520; and ¶Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591
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Contributed by Richard A. Flavell, February 9, 2004
Abstract
Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.
Footnotes
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↵ ** To whom correspondence should be addressed. E-mail: akiko.iwasaki{at}yale.edu.
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↵ † J.M.L. and L.A. contributed equally to this work.
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↵ ‡ Present address: Centre d'Immunologie de Marseille-Luminy (CIML), CNRS-INSERM, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.
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↵ ∥ The laboratories of A.I. and R.A.F. contributed equally to this work.
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Abbreviations: TLR, Toll-like receptor; VSV, vesicular stomatitis virus; DC, dendritic cell; pDC, plasmacytoid DC; ssRNA, single-stranded RNA; pfu, plaque-forming unit; HSV, herpes simplex virus; dsRNA, double-stranded RNA; TNFα, tumor necrosis factor α; RSV, respiratory syncytial virus.
- Copyright © 2004, The National Academy of Sciences
