tetano
Editor, Senior Moderator
J Virol. 2011 Feb 9. [Epub ahead of print]
Oligonucleotide Motifs That Disappear During the Evolution of Influenza in Humans Increase IFN-{alpha} secretion by Plasmacytoid Dendritic Cells.
Jimenez-Baranda S, Greenbaum B, Manches O, Handler J, Rabadan R, Levine A, Bhardwaj N.
New York University Langone Medical Center and New York University Cancer Institute, New York, USA; The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ; Department of Biomedical Informatics Center for Computational Biology and Bioinformatics, Columbia University College of Physicians and Surgeons, New York, USA.
Abstract
CpG motifs in an A/U context have been preferentially eliminated from classical H1N1 influenza virus genomes during virus evolution in humans. The hypothesis of the current work is that CpG-motifs in a uracil context represent sequence patterns with the capacity to induce an immune response, and the avoidance of this immunostimulatory signal is the reason for the observed preferential decline. To analyze the immunogenicity of these domains we used plasmacytoid dendritic cells (pDCs). pDCs express pattern-recognition receptors including Toll-like receptor 7 (TLR7), which recognizes guanosine- and uridine-rich viral ssRNA, including influenza virus ssRNA. The signaling through TLR7 results in the induction of inflammatory cytokines and type I interferon (IFN), essential processes for the induction of specific adaptive immune responses, and for mounting a robust antiviral response mediated by IFN-α. Secretion of IFN-α is also linked to the activation of other immune cells, potentially amplifying the effect of an initial IFN-α secretion. We therefore also examined the role of IFN-α-driven activation of NK cells as another source of selective pressure on the viral genome. We found direct evidence that CpG RNA motifs in U-rich context control pDC activation, and IFN-α-driven activation of NK cells, likely through Toll-like receptor 7. These data provide a potential explanation for the loss of CpGs motifs from avian influenza viruses as they adapt to mammalian hosts. The selective decrease of CpG motifs surrounded by U/A may be a viral strategy to avoid immune recognition, a strategy likely shared by highly expressed human immune genes.
PMID: 21307198 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21307198
Oligonucleotide Motifs That Disappear During the Evolution of Influenza in Humans Increase IFN-{alpha} secretion by Plasmacytoid Dendritic Cells.
Jimenez-Baranda S, Greenbaum B, Manches O, Handler J, Rabadan R, Levine A, Bhardwaj N.
New York University Langone Medical Center and New York University Cancer Institute, New York, USA; The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ; Department of Biomedical Informatics Center for Computational Biology and Bioinformatics, Columbia University College of Physicians and Surgeons, New York, USA.
Abstract
CpG motifs in an A/U context have been preferentially eliminated from classical H1N1 influenza virus genomes during virus evolution in humans. The hypothesis of the current work is that CpG-motifs in a uracil context represent sequence patterns with the capacity to induce an immune response, and the avoidance of this immunostimulatory signal is the reason for the observed preferential decline. To analyze the immunogenicity of these domains we used plasmacytoid dendritic cells (pDCs). pDCs express pattern-recognition receptors including Toll-like receptor 7 (TLR7), which recognizes guanosine- and uridine-rich viral ssRNA, including influenza virus ssRNA. The signaling through TLR7 results in the induction of inflammatory cytokines and type I interferon (IFN), essential processes for the induction of specific adaptive immune responses, and for mounting a robust antiviral response mediated by IFN-α. Secretion of IFN-α is also linked to the activation of other immune cells, potentially amplifying the effect of an initial IFN-α secretion. We therefore also examined the role of IFN-α-driven activation of NK cells as another source of selective pressure on the viral genome. We found direct evidence that CpG RNA motifs in U-rich context control pDC activation, and IFN-α-driven activation of NK cells, likely through Toll-like receptor 7. These data provide a potential explanation for the loss of CpGs motifs from avian influenza viruses as they adapt to mammalian hosts. The selective decrease of CpG motifs surrounded by U/A may be a viral strategy to avoid immune recognition, a strategy likely shared by highly expressed human immune genes.
PMID: 21307198 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21307198