The shortcomings of current direct-acting anti-viral therapy against human cytomegalovirus (HCMV) has led to interest in host-directed therapy. Here we re-examine the use of interferon proteins to inhibit HCMV replication utilizing both high and low passage strains of HCMV. Pre-treatment of cells with interferon alpha (IFNα) was required for robust and prolonged inhibition of both low and high passage HCMV strains, with no obvious toxicity, and was associated with an increased anti-viral state in HCMV-infected cells. Pre-treatment of cells with IFNα led to poor expression of HCMV immediate-early proteins from both high and low passage strains, which was associated with the presence of the anti-viral factor SUMO-PML. Inhibition of HCMV replication in the presence of IFNα involving ZAP proteins was HCMV strain-dependent, wherein a high passage HCMV strain was obviously restricted by ZAP and a low passage strain was not. This suggested that strain-specific combinations of anti-viral factors were involved in inhibition of HCMV replication in the presence of IFNα. Overall, this work further supports the development of strategies involving IFNα that may be useful to inhibit HCMV replication and highlights the complexity of the anti-viral response to HCMV in the presence of IFNα.

中文翻译：

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干扰素α抑制人巨细胞病毒复制可能涉及多种抗病毒因子

目前针对人巨细胞病毒（HCMV）的直接作用抗病毒疗法的缺点引起了人们对宿主导向疗法的兴趣。在这里，我们重新研究干扰素蛋白利用 HCMV 高传代株和低传代株抑制 HCMV 复制的用途。需要用干扰素α (IFNα) 对细胞进行预处理，以对低传代和高传代 HCMV 菌株进行强力和长时间的抑制，且无明显毒性，并且与 HCMV 感染细胞中抗病毒状态的增强相关。用 IFNα 预处理细胞导致高传代株和低传代株中 HCMV 立即早期蛋白的表达较差，这与抗病毒因子 SUMO-PML 的存在有关。涉及ZAP蛋白的IFNα存在下对HCMV复制的抑制是HCMV毒株依赖性的，其中高传代HCMV毒株明显受ZAP限制，而低传代毒株则不受ZAP限制。这表明，在 IFNα 存在的情况下，菌株特异性抗病毒因子组合参与了 HCMV 复制的抑制。总体而言，这项工作进一步支持了涉及 IFNα 的策略的开发，这些策略可能有助于抑制 HCMV 复制，并强调了在 IFNα 存在的情况下针对 HCMV 的抗病毒反应的复杂性。