Modulation of innate immune signaling by the secreted form of the West Nile virus NS1 glycoprotein
| Autor: | Clayton R. Morrison, Kristen R. Crook, Mindy Miller-Kittrell, Frank Scholle |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_treatment
viruses chemical and pharmacologic phenomena Viral Nonstructural Proteins Biology Toll like receptor Article Mice Virology medicine Animals Humans Myeloid Cells Luciferases Lymph node chemistry.chemical_classification Innate immunity Toll-like receptor Innate immune system Macrophages Flaviviridae virus diseases biochemical phenomena metabolism and nutrition Immunity Innate Specific Pathogen-Free Organisms Toll-Like Receptor 3 3. Good health Cell biology Mice Inbred C57BL Poly I-C medicine.anatomical_structure Cytokine chemistry Interleukin 15 TLR3 Signal transduction Glycoprotein West Nile virus Nonstructural protein HeLa Cells Signal Transduction |
| Zdroj: | Virology. :172-182 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2014.04.036 |
| Popis: | West Nile virus (WNV) employs several different strategies to escape the innate immune response. We have previously demonstrated that the WNV NS1 protein interferes with signal transduction from Toll-like receptor 3 (TLR3). NS1 is a glycoprotein that can be found intracellularly or associated with the plasma membrane. In addition, NS1 is secreted to high levels during flavivirus infections. We investigated whether the secreted form of NS1 inhibits innate immune signaling pathways in uninfected cells. Secreted NS1 (sNS1) was purified from supernatants of cells engineered to express the protein. Purified sNS1 associated with and repressed TLR3-induced cytokine production by HeLa cells, and inhibited signaling from TLR3 and other TLRs in bone marrow-derived macrophages and dendritic cells. Footpad administration of sNS1 showed the protein associated predominantly with macrophages and dendritic cells in the draining lymph node. Additionally, sNS1 significantly reduced TLR3 signaling and WNV replicon particle-mediated cytokine transcription in popliteal lymph nodes. |
| Databáze: | OpenAIRE |
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