Viral defective interfering particles (DIPs) with more than 90% of the genomic RNA (gRNA, ∼11 000 nucleotides) deleted have been detected in sera from dengue patients. The DIP RNA contains stem-loop structures in the 5' and 3' end, which may permit RNA replication in the same manner as dengue virus (DENV) gRNA. Transfection of DENV2 infected human hepatoma cells with DIP RNA (DIP-296) resulted in significant inhibition of virus replication. DIP-296 RNA inhibited DENV replication in a dose-dependent manner in several cell lines tested. The mechanism of inhibition by DIP RNA is unclear; however, our studies imply that the retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) mediated innate immune antiviral signaling pathways and direct interactions of DIP RNA with viral replication proteins may be involved. The latter is supported by in vitro RNA electrophoretic mobility shift assays (REMSAs), which show that DIP RNA can bind directly to the DENV nonstructural proteins NS3 and NS5.

中文翻译：

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来自登革热2型病毒的亚基因组RNA抑制了登革热病毒基因组的复制，并与病毒编码的NS3和NS5蛋白相互作用。

在登革热患者的血清中检测到病毒缺陷干扰颗粒（DIP），其中有90％以上的基因组RNA（gRNA，约11000个核苷酸）被删除。DIP RNA在5'和3'端含有茎环结构，可以与登革热病毒（DENV）gRNA相同的方式进行RNA复制。用DIP RNA（DIP-296）转染DENV2感染的人肝癌细胞可显着抑制病毒复制。DIP-296 RNA在几种受试细胞系中以剂量依赖性方式抑制DENV复制。DIP RNA抑制的机制尚不清楚；然而，我们的研究表明，视黄酸诱导基因1（RIG-I）和黑色素瘤分化相关基因5（MDA5）介导的先天免疫抗病毒信号通路以及DIP RNA与病毒复制蛋白的直接相互作用。后者得到体外RNA电泳迁移率变动分析（REMSA）的支持，该分析表明DIP RNA可以直接结合DENV非结构蛋白NS3和NS5。