Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness.
Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness.
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DOI：
10.1126/science.aab3369
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发表时间：
2015-10-09
期刊：
影响因子：
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通讯作者：
Ooi EE
中科院分区：
文献类型：
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作者：
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
登革热病毒（DENV）感染的全球传播增加了病毒遗传多样性，其中一些似乎与更大的流行潜力有关。然而，在流行病学环境中控制病毒适应性的机制仍然不明确。我们确定了外来优势 (PR-2B) DENV 血清型 2 (DENV-2) 分支的适应性决定因素，该分支在 1994 年波多黎各流行期间出现，并取代了地方性 (PR-1) DENV-2 分支。 PR-2B DENV-2 在复制过程中产生的亚基因组黄病毒 RNA (sfRNA) 水平相对于基因组 RNA 有所增加。 PR-2B sfRNA 显示出与三联基序 25 (TRIM25) 去泛素化的序列依赖性结合和预防，这对于持续和扩增视黄酸诱导基因 1 (RIG-I) 诱导的 I 型干扰素表达至关重要。我们的研究结果表明，病毒 RNA 与宿主蛋白之间存在独特的相互作用，可以逃避先天免疫反应，从而提高流行病学适应性。
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.