Université de Paris, INSERM U976, Insight Team, F-75010, Paris, France; Assistance-Publique des Hôpitaux de Paris, Microbiology Department, Virology Unit, Saint Louis Hospital, F-75010, Paris, France.
Assistance-Publique des Hôpitaux de Paris, Microbiology Department, Virology Unit, Saint Louis Hospital, F-75010, Paris, France.
Antiviral Res. 2020 Oct;182:104872. doi: 10.1016/j.antiviral.2020.104872. Epub 2020 Aug 5.
Human adenovirus (HAdV) infections are associated with a high morbidity and mortality in transplant patients requiring the use of antiviral treatments. Brincidofovir (BCV), a cytidine analog, inhibits HAdV replication through viral DNA elongation termination and likely through other mechanisms. To elucidate if BCV regulates cellular antiviral pathways, we analyzed its impact on HAdV-infected and non-HAdV-infected lung epithelial cells.
We assessed the cellular and viral transcriptome of A549 cells infected and non-infected with HAdV C5 and treated or non-treated with BCV by RNAseq after 72 h.
BCV treatment of HAdV infected cells resulted in a profound decrease of viral transcription associated with a relative overexpression of the early genes E1A and E4 and of the late gene L1. BCV had also a profound impact on A549 cells' transcriptome. Ontologic analysis revealed an effect of BCV on several pathways known to interact with adenovirus replication as mTor signalling and Wnt pathways. A549 cells treated with BCV demonstrated a significant inhibition of the biological function of "viral replication" including 25 dysregulated genes involved in inflammation pathways.
We demonstrated that BCV alters viral gene expression and promotes the expression of antiviral cellular pathways in A549 cells. These results provide new insights how to interfere with cellular pathways to control HAdV infections.
人腺病毒（HAdV）感染与移植患者的高发病率和死亡率相关，需要使用抗病毒治疗。布西福韦（BCV）是一种胞嘧啶类似物，通过病毒 DNA 延长终止和可能通过其他机制抑制 HAdV 复制。为了阐明 BCV 是否调节细胞抗病毒途径，我们分析了其对 HAdV 感染和非 HAdV 感染的肺上皮细胞的影响。
我们通过 RNAseq 在 72 小时后评估了 HAdV C5 感染和未感染的 A549 细胞的细胞和病毒转录组，以及用 BCV 处理和未处理的细胞。
BCV 处理 HAdV 感染细胞导致病毒转录的显著下降，与早期基因 E1A 和 E4 以及晚期基因 L1 的相对过表达相关。BCV 对 A549 细胞的转录组也有深远的影响。本体分析显示，BCV 对与腺病毒复制相互作用的几个途径有影响，如 mTor 信号和 Wnt 途径。用 BCV 处理的 A549 细胞显示出“病毒复制”的生物学功能显著抑制，包括 25 个涉及炎症途径的失调基因。
我们证明了 BCV 改变了病毒基因的表达，并促进了 A549 细胞中抗病毒细胞途径的表达。这些结果提供了新的见解，如何干扰细胞途径来控制 HAdV 感染。
