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ATO (Arsenic Trioxide) Effects on Promyelocytic Leukemia Nuclear Bodies Reveals Antiviral Intervention Capacity.
Advanced Science ( IF 14.3 ) Pub Date : 2020-02-27 , DOI: 10.1002/advs.201902130 Samuel Hofmann 1 , Julia Mai 1 , Sawinee Masser 1 , Peter Groitl 1 , Alexander Herrmann 2 , Thomas Sternsdorf 3 , Ruth Brack-Werner 2 , Sabrina Schreiner 1, 2
Advanced Science ( IF 14.3 ) Pub Date : 2020-02-27 , DOI: 10.1002/advs.201902130 Samuel Hofmann 1 , Julia Mai 1 , Sawinee Masser 1 , Peter Groitl 1 , Alexander Herrmann 2 , Thomas Sternsdorf 3 , Ruth Brack-Werner 2 , Sabrina Schreiner 1, 2
Affiliation
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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：
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。
人类腺病毒（HAdV）与胃肠炎、角结膜炎、肺炎、肝炎和脑炎等临床症状相关。在缺乏保护性免疫力的情况下，如同种异体骨髓移植患者，HAdV 感染可能会致命。令人震惊的是，最近报道了各种高致病性、嗜肺性HAdV类型的爆发，导致严重和致命的呼吸道疾病。目前仍缺乏治疗HAdV感染的有效药物。批准用于其他适应症的药物的重新利用是开发新抗病毒疗法的一个有价值的替代方案，并且比从头开发风险和成本更低。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，ATO 被证明是 HAdV 的有效抑制剂。 ATO 治疗通过减少早幼粒细胞白血病 (PML) 核体（HAdV 复制的重要亚核结构）的数量和完整性来阻断病毒表达和复制。用小型泛素样修饰物 (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，表明 ATO 干扰了对 HAdV 复制至关重要的蛋白质的 SUMO 化。结论是，ATO 针对 HAdV 复制的关键细胞过程，并且与抗病毒干预策略的开发相关。
更新日期：2020-04-21
中文翻译：
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。
人类腺病毒（HAdV）与胃肠炎、角结膜炎、肺炎、肝炎和脑炎等临床症状相关。在缺乏保护性免疫力的情况下，如同种异体骨髓移植患者，HAdV 感染可能会致命。令人震惊的是，最近报道了各种高致病性、嗜肺性HAdV类型的爆发，导致严重和致命的呼吸道疾病。目前仍缺乏治疗HAdV感染的有效药物。批准用于其他适应症的药物的重新利用是开发新抗病毒疗法的一个有价值的替代方案，并且比从头开发风险和成本更低。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，ATO 被证明是 HAdV 的有效抑制剂。 ATO 治疗通过减少早幼粒细胞白血病 (PML) 核体（HAdV 复制的重要亚核结构）的数量和完整性来阻断病毒表达和复制。用小型泛素样修饰物 (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，表明 ATO 干扰了对 HAdV 复制至关重要的蛋白质的 SUMO 化。结论是，ATO 针对 HAdV 复制的关键细胞过程，并且与抗病毒干预策略的开发相关。
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