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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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; Ooi, EE

Published Date

  • October 2015

Published In

Volume / Issue

  • 350 / 6257

Start / End Page

  • 217 - 221

PubMed ID

  • 26138103

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.aab3369

Language

  • eng