Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness

Gayathri Manokaran, Esteban Finol, Chunling Wang, Jayantha Gunaratne, Justin Bahl, Eugenia Z. Ong, Hwee Cheng Tan, October M. Sessions, Alex M. Ward, Duane J. Gubler, Eva Harris, Mariano Garcia-Blanco, Eng Eong Ooi

Research output: Contribution to journalArticle

165 Scopus citations

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 sequencedependent 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.

Original languageEnglish (US)
Pages (from-to)217-221
Number of pages5
JournalScience
Volume350
Issue number6257
DOIs
StatePublished - Oct 9 2015

ASJC Scopus subject areas

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    Manokaran, G., Finol, E., Wang, C., Gunaratne, J., Bahl, J., Ong, E. Z., Tan, H. C., Sessions, O. M., Ward, A. M., Gubler, D. J., Harris, E., Garcia-Blanco, M., & Ooi, E. E. (2015). Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness. Science, 350(6257), 217-221. https://doi.org/10.1126/science.aab3369