The novel lncRNA ALPHA specifically targets chikungunya virus to control infection

We set out to determine whether lncRNAs can contribute to additional antiviral immune strategies independently of canonical innate signaling. High-throughput genetic screening of 2200 human lncRNAs led to the identification of the cytoplasmic antiviral lncRNA Antiviral LncRNA Prohibiting Human Alphaviruses (ALPHA) which is transcriptionally induced by alphaviruses and functions independently of IFN to specifically inhibit the replication of CHIKV and its closest relative, O'nyong'nyong virus (ONNV), but not other viruses. Furthermore, we showed that ALPHA interacts with CHIKV genomic RNA and restrains viral RNA replication. Together, our findings reveal that ALPHA and potentially other lncRNAs can mediate non-canonical antiviral immune responses against specific viral pathogens. Overall design: RNA sequencing from human brain microvascular endothelial cells (HBMEC) in the presence and absence of chikungunya virus (CHIKV) or the phylogenetically disparate arbovirus, Zika virus (ZIKV)

本研究旨在探究长链非编码RNA（long non-coding RNA，lncRNA）能否独立于经典天然免疫信号通路，参与额外的抗病毒免疫策略。我们通过对2200种人类长链非编码RNA开展高通量遗传筛选，鉴定出一种胞质抗病毒长链非编码RNA——抗人类甲病毒lncRNA（Antiviral LncRNA Prohibiting Human Alphaviruses，ALPHA）。该分子可由甲病毒转录诱导，且不依赖干扰素（Interferon，IFN）发挥功能，能够特异性抑制基孔肯雅病毒（chikungunya virus，CHIKV）及其近缘病毒奥尼永尼永病毒（O'nyong'nyong virus，ONNV）的复制，却对其他病毒无效。此外，本研究证实ALPHA可与基孔肯雅病毒基因组RNA结合，并抑制病毒RNA的复制过程。综上，本研究结果表明，ALPHA以及其他潜在的长链非编码RNA，可介导针对特定病毒病原体的非经典抗病毒免疫应答。整体实验设计：对分别处于基孔肯雅病毒（chikungunya virus，CHIKV）感染/未感染，以及系统发育差异显著的虫媒病毒（arthropod-borne virus，arbovirus）寨卡病毒（Zika virus，ZIKV）感染/未感染状态下的人类脑微血管内皮细胞（human brain microvascular endothelial cells，HBMEC）进行RNA测序。