Azithromycin Protects against Zika Virus Infection by Upregulating Virus-Induced Type I and III Interferon Responses
Azithromycin Protects against Zika Virus Infection by Upregulating Virus-Induced Type I and III Interferon Responses
复制标题
阿奇霉素通过上调病毒诱导的 I 型和 III 型干扰素反应来预防寨卡病毒感染
DOI：
10.1128/aac.00394-19
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发表时间：
2019-12-01
影响因子：
4.9
通讯作者：
Cheng, Genhong
中科院分区：
文献类型：
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作者：
Li, Chunfeng;Zu, Shulong;Cheng, Genhong
阿奇霉素（AZM）是一种广泛使用的抗生素，具有额外的抗病毒和抗炎特性，但仍知之甚少。虽然寨卡病毒（ZIKV）对全球健康构成重大威胁，但目前还没有针对它的疫苗或有效治疗方法。在这里，我们报告了AZM通过靶向病毒生命周期的后期阶段有效抑制ZIKV感染。此外，AZM响应于ZIKV感染上调宿主I型和III型干扰素及其若干下游干扰素刺激基因的表达。特别是，我们发现AZM上调了MDA 5和RIG-I（ZIKV感染诱导的病原体识别受体）的表达，并增加了磷酸化TBK 1和IRF 3的水平。有趣的是，AZM处理上调TBK 1的磷酸化，而不诱导IRF 3本身的磷酸化。这些发现强调了AZM作为一种广泛的抗病毒剂的潜在用途，以对抗病毒感染并预防毁灭性的ZIKV相关临床结果，如先天性小头畸形。
Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Here, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle. In addition, AZM upregulates the expression of host type I and III interferons and several of their downstream interferon-stimulated genes in response to ZIKV infection. In particular, we found that AZM upregulated the expression of MDA5 and RIG-I (pathogen recognition receptors induced by ZIKV infection) and increased the levels of phosphorylated TBK1 and IRF3. Interestingly, AZM treatment upregulated the phosphorylation of TBK1 without inducing the phosphorylation of IRF3 by itself. These findings highlight the potential use of AZM as a broad antiviral agent to combat viral infection and to prevent devastating ZIKV-associated clinical outcomes, such as congenital microcephaly.