PDF(Pubmed)
Abstract：
Subgenomic flaviviral RNAs (sfRNAs) are small non-coding products of the incomplete degradation of viral genomic RNA. They accumulate during flaviviral infection and have been associated with many functional roles inside the host cell. Studies so far have demonstrated that sfRNA plays a crucial role in determining West Nile virus (WNV) pathogenicity. However, its modulatory role on neuronal homeostasis has not been studied in depth. In this study, we investigated the mechanism of sfRNA biosynthesis and its importance for WNV replication in neuronal cells. We found that sfRNA1 is functionally redundant for both replication and translation of WNV. However, the concurrent absence of sfRNA1 and sfRNA2 species is detrimental for the survival of the virus. Differential expression analysis on RNA-seq data from WT and ΔsfRNA replicon cell lines revealed transcriptional changes induced by sfRNA and identified a number of putative targets. Overall, it was shown that sfRNA contributes to the viral evasion by suppressing the interferon-mediated antiviral response. An additional differential expression analysis among replicon and control Neuro2A cells also clarified the transcriptional changes that support WNV replication in neuronal cells. Increased levels of translation and oxidative phosphorylation, post-translational modification processes, and activated DNA repair pathways were observed in replicon cell lines, while developmental processes such as axonal growth were deficient.
摘要：
亚基因组黄病毒RNA(sfRNA)是病毒基因组RNA不完全降解的小的非编码产物。它们在黄病毒感染期间积累，并与宿主细胞内的许多功能作用有关。迄今为止的研究表明，sfRNA在确定西尼罗河病毒（WNV）的致病性中起着至关重要的作用。然而,其对神经元稳态的调节作用尚未得到深入研究。在这项研究中,我们研究了sfRNA生物合成的机制及其对神经元细胞中WNV复制的重要性。我们发现sfRNA1对于WNV的复制和翻译都是功能冗余的。然而,同时缺乏sfRNA1和sfRNA2对病毒的存活是有害的。对WT和ΔsfRNA复制子细胞系的RNA-seq数据的差异表达分析揭示了sfRNA诱导的转录变化，并鉴定了许多推定的靶标。总的来说,研究表明，sfRNA通过抑制干扰素介导的抗病毒反应而有助于病毒逃避。复制子和对照Neuro2A细胞之间的额外差异表达分析也阐明了支持神经元细胞中WNV复制的转录变化。翻译和氧化磷酸化水平增加，翻译后修饰过程，在复制子细胞系中观察到激活的DNA修复途径，而轴突生长等发育过程不足。
