Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness.
Journal Article (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 9, 2015
Published In
Volume / Issue
- 350 / 6257
Start / End Page
- 217 - 221
PubMed ID
- 26138103
Pubmed Central ID
- PMC4824004
Electronic International Standard Serial Number (EISSN)
- 1095-9203
Digital Object Identifier (DOI)
- 10.1126/science.aab3369
Language
- eng
Conference Location
- United States