51. Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness.
- Author
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Manokaran G, Finol E, Wang C, Gunaratne J, Bahl J, Ong EZ, Tan HC, Sessions OM, Ward AM, Gubler DJ, Harris E, Garcia-Blanco MA, and Ooi EE
- Subjects
- Animals, Biodiversity, Chlorocebus aethiops, DEAD Box Protein 58, DEAD-box RNA Helicases metabolism, Dengue epidemiology, Dengue Virus genetics, Humans, Interferon Type I antagonists & inhibitors, Interferon Type I genetics, Puerto Rico epidemiology, RNA, Viral genetics, Receptors, Immunologic, Tripartite Motif Proteins, Ubiquitination, Vero Cells, Dengue immunology, Dengue virology, Dengue Virus physiology, Immunity, Innate, Interferon Type I immunology, RNA, Viral metabolism, Transcription Factors metabolism, Ubiquitin-Protein Ligases metabolism, Virus Replication
- Abstract
The global spread of dengue virus (DENV) infections has increased viral genetic diversity, some of which appears associated with greater epidemic potential. The mechanisms governing viral fitness in epidemiological settings, however, remain poorly defined. We identified a determinant of fitness in a foreign dominant (PR-2B) DENV serotype 2 (DENV-2) clade, which emerged during the 1994 epidemic in Puerto Rico and replaced an endemic (PR-1) DENV-2 clade. The PR-2B DENV-2 produced increased levels of subgenomic flavivirus RNA (sfRNA) relative to genomic RNA during replication. PR-2B sfRNA showed sequence-dependent binding to and prevention of tripartite motif 25 (TRIM25) deubiquitylation, which is critical for sustained and amplified retinoic acid-inducible gene 1 (RIG-I)-induced type I interferon expression. Our findings demonstrate a distinctive viral RNA-host protein interaction to evade the innate immune response for increased epidemiological fitness., (Copyright © 2015, American Association for the Advancement of Science.)
- Published
- 2015
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