Zika Virus-Encoded NS2A and NS4A Strongly Downregulate NF-κB Promoter Activity
| Autor: | Jeong Yoon Lee, Thi Thuy Ngan Nguyen, Jinjong Myoung |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Cell signaling Interferon-Induced Helicase IFIH1 viruses Down-Regulation Gene Expression Viral Nonstructural Proteins 01 natural sciences Applied Microbiology and Biotechnology Virus Zika virus Interferon 010608 biotechnology medicine Animals Humans Receptors Immunologic Promoter Regions Genetic NS3 Innate immune system biology Zika Virus Infection NF-kappa B MDA5 General Medicine Zika Virus biology.organism_classification Virology Immunity Innate Flavivirus Culicidae HEK293 Cells DEAD Box Protein 58 Brazil Biotechnology medicine.drug Signal Transduction |
| Zdroj: | Journal of microbiology and biotechnology. 30(11) |
| ISSN: | 1738-8872 |
| Popis: | Since Zika virus (ZIKV) was first detected in Uganda in 1947, serious outbreaks have occurred globally in Yap Island, French Polynesia and Brazil. Even though the number of infections and spread of ZIKV have risen sharply, the pathogenesis and replication mechanisms of ZIKV have not been well studied. ZIKV, a recently highlighted Flavivirus, is a mosquito-borne emerging virus causing microcephaly and the Guillain-Barre syndrome in fetuses and adults, respectively. ZIKV polyprotein consists of three structural proteins named C, prM and E and seven nonstructural proteins named NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 in an 11-kb single-stranded positive sense RNA genome. The function of individual ZIKV genes on the host innate immune response has barely been studied. In this study, we investigated the modulations of the NF-κB promoter activity induced by the MDA5/RIG-I signaling pathway. According to our results, two nonstructural proteins, NS2A and NS4A, dramatically suppressed the NF-κB promoter activity by inhibiting signaling factors involved in the MDA5/RIG-I signaling pathway. Interestingly, NS2A suppressed all components of MDA5/RIG-I signaling pathway, but NS4A inhibited most signaling molecules, except IKKe and IRF3-5D. In addition, both NS2A and NS4A downregulated MDA5-induced NF-κB promoter activity in a dosedependent manner. Taken together, our results suggest that NS2A and NS4A signifcantly antagonize MDA5/RIG-I-mediated NF-κB production, and these proteins seem to be controlled by different mechanisms. This study could help understand the mechanisms of how ZIKV controls innate immune responses and may also assist in the development of ZIKV-specific therapeutics. |
| Databáze: | OpenAIRE |
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