Inhibition of Interferon Signaling by the New York 99 Strain and Kunjin Subtype of West Nile Virus Involves Blockage of STAT1 and STAT2 Activation by Nonstructural Proteins
| Autor: | Alexander A. Khromykh, Vladislav V. Mokhonov, Xiang Ju Wang, Wen Jun Liu, Richard E. Randall, Pei Yong Shi |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
viruses
Immunology Viral Nonstructural Proteins Microbiology Virus Cell Line Kunjin virus Interferon Virology Chlorocebus aethiops medicine Animals Humans Vero Cells NS3 biology STAT2 Transcription Factor biology.organism_classification Molecular biology Virus-Cell Interactions DNA-Binding Proteins Flavivirus STAT1 Transcription Factor Gene Expression Regulation Insect Science Trans-Activators Vero cell Phosphorylation Interferons Signal transduction West Nile virus Signal Transduction medicine.drug |
| Zdroj: | Journal of Virology. 79:1934-1942 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.79.3.1934-1942.2005 |
| Popis: | The interferon (IFN) response is the first line of defense against viral infections, and the majority of viruses have developed different strategies to counteract IFN responses in order to ensure their survival in an infected host. In this study, the abilities to inhibit IFN signaling of two closely related West Nile viruses, the New York 99 strain (NY99) and Kunjin virus (KUN), strain MRM61C, were analyzed using reporter plasmid assays, as well as immunofluorescence and Western blot analyses. We have demonstrated that infections with both NY99 and KUN, as well as transient or stable transfections with their replicon RNAs, inhibited the signaling of both alpha/beta IFN (IFN-α/β) and gamma IFN (IFN-γ) by blocking the phosphorylation of STAT1 and its translocation to the nucleus. In addition, the phosphorylation of STAT2 and its translocation to the nucleus were also blocked by KUN, NY99, and their replicons in response to treatment with IFN-α. IFN-α signaling and STAT2 translocation to the nucleus was inhibited when the KUN nonstructural proteins NS2A, NS2B, NS3, NS4A, and NS4B, but not NS1 and NS5, were expressed individually from the pcDNA3 vector. The results clearly demonstrate that both NY99 and KUN inhibit IFN signaling by preventing STAT1 and STAT2 phosphorylation and identify nonstructural proteins responsible for this inhibition. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|