| Literature DB >> 26138103 |
Gayathri Manokaran1, Esteban Finol2, Chunling Wang3, Jayantha Gunaratne4, Justin Bahl5, Eugenia Z Ong6, Hwee Cheng Tan6, October M Sessions6, Alex M Ward6, Duane J Gubler6, Eva Harris3, Mariano A Garcia-Blanco7, Eng Eong Ooi8.
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.Entities:
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Year: 2015 PMID: 26138103 PMCID: PMC4824004 DOI: 10.1126/science.aab3369
Source DB: PubMed Journal: Science ISSN: 0036-8075 Impact factor: 47.728