Yao Wenxia, Pan Jinghui, Liu Zhaoyu, Dong Zhijie, Liang Min, Xia Shu, Xiao Yao, Cai Xiaodan, Peng Tao, Zhou Xinke, Cai Hua
The Fifth Affiliated Hospital of Guangzhou Medical Universitygrid.410737.6Guangzhou Medical University, grid.410737.6, Guangzhou Medical University, Guangzhou, China.
Guangzhou Hoffmann Institute of Immunology, College of Basic Sciences, Guangzhou Medical Universitygrid.410737.6, Guangzhou, China.
mBio. 2021 Dec 21;12(6):e0307521. doi: 10.1128/mBio.03075-21. Epub 2021 Dec 7.
Circular RNAs (circRNAs) are a new class of noncoding RNAs that have gained increased attention. DNA virus infections have been reported to induce modifications in cellular circRNA transcriptomes and express viral circRNAs. However, the identification and expression of cellular and viral circRNAs are unknown in the context of respiratory syncytial virus (RSV), a human RNA virus with no effective treatments or vaccines. Here, we report a comprehensive identification of the cellular and viral circRNAs induced by RSV infection in A549 cells with high-throughput sequencing. In total, 53,719 cellular circRNAs and 2,280 differentially expressed cellular circRNAs were identified. Trend analysis further identified three significant expression pattern clusters, which were related to the antiviral immune response according to gene enrichment analysis. Subsequent results showed that not only RSV infection but also poly(I·C) treatment and another RNA virus infection induced the upregulation of the top 10 circRNAs from the focused cluster. The top 10 circRNAs generally inhibit RSV replication in turn. Moreover, 1,254 viral circRNAs were identified by the same circRNA sequencing. The induced expression of viral circRNAs by RSV infection was found not only in A549 cells but also in HEp-2 cells. Additionally, we profiled the general characteristics of both cellular and viral circRNAs such as back-splicing signals, etc. Collectively, RSV infection induced the differential expression of cellular circRNAs, some of which affected RSV infection, and RSV also expressed viral circRNAs. Our study reveals novel layers of host-RSV interactions and identifies cellular or viral circRNAs that may be novel therapeutic targets or biomarkers. Noncoding RNAs (ncRNAs) demonstrate substantial roles in cell-virus interactions. Circular RNAs (circRNAs) are a newly identified class of ncRNAs that have gained increased attention recently. DNA virus infections have been reported to induce modifications in cellular circRNA transcriptomes and express viral circRNAs. However, the identification and expression of cellular and viral circRNAs are unknown in the context of respiratory syncytial virus (RSV), a human RNA virus with no effective treatments or vaccines. Here, we report a comprehensive identification of the cellular and viral circRNAs induced by RSV infection by high-throughput sequencing. We revealed that RSV infection induces the differential expression of cellular circRNAs, some of which affected RSV infection, and that RSV also expresses viral circRNAs. Our study reveals novel layers of host-RSV interactions and identifies cellular or viral circRNAs that may be novel therapeutic targets or biomarkers.
环状RNA（circRNAs）是一类新的非编码RNA，已受到越来越多的关注。据报道，DNA病毒感染可诱导细胞circRNA转录组发生改变并表达病毒circRNAs。然而，在呼吸道合胞病毒（RSV）感染的情况下，细胞和病毒circRNAs的鉴定和表达尚不清楚。RSV是一种人类RNA病毒，目前尚无有效的治疗方法或疫苗。在此，我们通过高通量测序全面鉴定了RSV感染A549细胞后诱导产生的细胞和病毒circRNAs。总共鉴定出53,719个细胞circRNAs和2,280个差异表达的细胞circRNAs。趋势分析进一步确定了三个显著的表达模式簇，根据基因富集分析，这些簇与抗病毒免疫反应相关。随后的结果表明，不仅RSV感染，而且聚肌胞苷酸（poly(I·C)）处理和另一种RNA病毒感染均能诱导聚焦簇中排名前10的circRNAs上调。排名前10的circRNAs通常依次抑制RSV复制。此外，通过相同的circRNA测序鉴定出1,254个病毒circRNAs。发现RSV感染诱导的病毒circRNAs表达不仅在A549细胞中存在，在HEp-2细胞中也存在。此外，我们还分析了细胞和病毒circRNAs的一般特征，如反向剪接信号等。总体而言，RSV感染诱导了细胞circRNAs的差异表达，其中一些影响了RSV感染，并且RSV还表达病毒circRNAs。我们的研究揭示了宿主与RSV相互作用的新层面，并鉴定出可能成为新型治疗靶点或生物标志物的细胞或病毒circRNAs。非编码RNA（ncRNAs）在细胞与病毒的相互作用中发挥着重要作用。环状RNA（circRNAs）是一类新发现的ncRNAs，最近受到了越来越多的关注。据报道，DNA病毒感染可诱导细胞circRNA转录组发生改变并表达病毒circRNAs。然而，在呼吸道合胞病毒（RSV）感染的情况下，细胞和病毒circRNAs的鉴定和表达尚不清楚。RSV是一种人类RNA病毒，目前尚无有效的治疗方法或疫苗。在此，我们通过高通量测序全面鉴定了RSV感染诱导产生的细胞和病毒circRNAs。我们发现RSV感染诱导了细胞circRNAs的差异表达，其中一些影响了RSV感染，并且RSV还表达病毒circRNAs。我们的研究揭示了宿主与RSV相互作用的新层面，并鉴定出可能成为新型治疗靶点或生物标志物的细胞或病毒circRNAs。
