Human adenoviruses (HAdV) are associated with clinical symptoms such as gastroenteritis, keratoconjunctivitis, pneumonia, hepatitis, and encephalitis. In the absence of protective immunity, as in allogeneic bone marrow transplant patients, HAdV infections can become lethal. Alarmingly, various outbreaks of highly pathogenic, pneumotropic HAdV types have been recently reported, causing severe and lethal respiratory diseases. Effective drugs for treatment of HAdV infections are still lacking. The repurposing of drugs approved for other indications is a valuable alternative for the development of new antiviral therapies and is less risky and costly than de novo development. Arsenic trioxide (ATO) is approved for treatment of acute promyelocytic leukemia. Here, it is shown that ATO is a potent inhibitor of HAdV. ATO treatment blocks virus expression and replication by reducing the number and integrity of promyelocytic leukemia (PML) nuclear bodies, important subnuclear structures for HAdV replication. Modification of HAdV proteins with small ubiquitin-like modifiers (SUMO) is also key to HAdV replication. ATO reduces levels of viral SUMO-E2A protein, while increasing SUMO-PML, suggesting that ATO interferes with SUMOylation of proteins crucial for HAdV replication. It is concluded that ATO targets cellular processes key to HAdV replication and is relevant for the development of antiviral intervention strategies.

中文翻译：

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ATO（三氧化二砷）对早幼粒细胞白血病核体的影响揭示了抗病毒干预能力。

人腺病毒（HAdV）与胃肠道炎，角膜结膜炎，肺炎，肝炎和脑炎等临床症状相关。如同种异体骨髓移植患者一样，在缺乏保护性免疫的情况下，HAdV感染可能致命。令人震惊的是，最近已报道了多种高致病性，嗜气性HAdV暴发，引起严重和致命的呼吸道疾病。仍然缺乏用于治疗HAdV感染的有效药物。重新批准已批准用于其他适应症的药物是开发新的抗病毒疗法的有价值的替代方法，并且比从头开发的风险和成本更低。三氧化二砷（ATO）被批准用于治疗急性早幼粒细胞白血病。在此，表明ATO是HAdV的有效抑制剂。ATO治疗可通过减少早幼粒细胞白血病（PML）核小体（HAdV复制的重要亚核结构）的数量和完整性来阻止病毒表达和复制。用小的泛素样修饰剂（SUMO）修饰HAdV蛋白也是HAdV复制的关键。ATO降低了病毒SUMO-E2A蛋白的水平，同时增加了SUMO-PML，这表明ATO干扰了HAdV复制至关重要的蛋白的SUMOylation。结论是，ATO靶向于HAdV复制关键的细胞过程，并且与抗病毒干预策略的发展有关。用小的泛素样修饰剂（SUMO）修饰HAdV蛋白也是HAdV复制的关键。ATO降低了病毒SUMO-E2A蛋白的水平，同时增加了SUMO-PML，这表明ATO干扰了HAdV复制至关重要的蛋白的SUMOylation。结论是，ATO靶向于HAdV复制关键的细胞过程，并且与抗病毒干预策略的发展有关。用小的泛素样修饰剂（SUMO）修饰HAdV蛋白也是HAdV复制的关键。ATO降低了病毒SUMO-E2A蛋白的水平，同时增加了SUMO-PML，这表明ATO干扰了HAdV复制至关重要的蛋白的SUMOylation。结论是，ATO靶向于HAdV复制关键的细胞过程，并且与抗病毒干预策略的发展有关。