Human adenoviruses (HAdVs) usually cause mild respiratory infections, but they can also lead to fatal outcomes for immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for medical use. A better understanding of the nature of virus-host interactions during infection is beneficial to the discovery of potential antiviral targets and new antiviral drugs. In this study, a time-course transcriptome analysis of HAdV-infected human lung epithelial cells (A549 cells) was performed to investigate virus–host interactions, and several key host molecules involved in the HAdV infection process were identified. The RARβ (retinoic acid receptor β) molecule, one of the upstream regulatory factors of differentially expressed genes (DEGs), played important roles in HAdV replication. The results of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed that RARβ mRNA and protein were downregulated by HAdV infection in the A549 cells. The knockdown of RARβ by RARβ siRNA increased the HAdV production and the overexpression of RARβ decreased the HAdV production. Furthermore, FDA-approved Tazarotene, which is an RAR selective agonist with relatively more selectivity for RARβ, was found to inhibit HAdV replication in vitro. Taken together, our study presents a key host molecule in adenovirus infection, which could be developed as a potential host target to an anti-adenovirus drug. In addition, this study provides evidence for the re-exploitation of an FDA-approved small molecule for therapeutic applications in adenovirus replication.

人腺病毒（HAdV）通常引起轻度呼吸道感染，但它们也可能导致免疫抑制患者致命。不幸的是，还没有批准用于医疗用途的特定抗HAdV药物。更好地了解感染过程中病毒-宿主相互作用的性质有利于发现潜在的抗病毒靶标和新的抗病毒药物。在这项研究中，进行了HAdV感染的人肺上皮细胞（A549细胞）的时程转录组分析，以研究病毒与宿主之间的相互作用，并鉴定了参与HAdV感染过程的几个关键宿主分子。RARβ（视黄酸受体β）分子是差异表达基因（DEG）的上游调节因子之一，在HAdV复制中起着重要作用。逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹的结果表明，HAdV感染可导致A549细胞中RARβmRNA和蛋白下调。RARβsiRNA敲低RARβ会增加HAdV的产生，而RARβ的过表达会降低HAdV的产生。此外，还发现了FDA批准的他扎罗汀，它是一种RAR选择性激动剂，对RARβ具有相对更高的选择性，可抑制HAdV复制。体外。综上所述，我们的研究提出了腺病毒感染中的关键宿主分子，可以将其开发为抗腺病毒药物的潜在宿主靶标。此外，这项研究为FDA批准的小分子在腺病毒复制中的治疗应用提供了新的证据。