ADP-ribosyltransferase PARP11 suppresses Zika virus in synergy with PARP12.

ADP-ribosyltransferase PARP11 suppresses Zika virus in synergy with PARP12.
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DOI:
10.1186/s13578-021-00628-y
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发表时间:
2021-06-29
期刊:
影响因子:
7.5
通讯作者:
Cheng G
Cheng G
中科院分区:
生物学2区
文献类型:
--
作者:
Li L;Shi Y;Li S;Liu J;Zu S;Xu X;Gao M;Sun N;Pan C;Peng L;Yang H;Cheng G

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寨卡病毒(ZIKV)感染和ZIKV流行一直在世界范围内默默地持续传播,其相关的小头畸形和其他严重的先天性神经系统并发症对公共卫生构成重大的全球威胁。宿主细胞中对ZIKV感染的I型干扰素应答通过诱导干扰素刺激的基因(ISG)的表达来抑制病毒复制。该研究旨在证明PARP 11的抗ZIKV机制。构建PARP 11敲除和过表达A549细胞系以评估PARP 11的抗ZIKV功能。构建PARP 11 −/−、PARP 12 −/−和PARP 11 −/− PARP 12 −/− HEK 293 T细胞系,以解释PARP 11和PARP 12对NS 1和NS 3蛋白降解的协同作用。通过Western blotting、免疫荧光和免疫沉淀分析来说明PARP 11和PARP 12之间的相互作用。在WT细胞中,PARP 11的mRNA和蛋白水平均被诱导,但在IFNα或IFNβ刺激和ZIKV感染后,IFNAR 1 −/−细胞中未被诱导。ZIKV复制在表达PARP 11的细胞中受到抑制,但在PARP 11 −/−细胞中得到增强。PARP 11独立于其自身PARP酶活性抑制ZIKV。PARP 11与PARP 12相互作用并促进PARP 12介导的ZIKV NS 1和NS 3蛋白降解。我们鉴定了ADP-核糖基转移酶PARP 11作为抗ZIKV ISG,并发现它与PARP 12合作增强ZIKV NS 1和NS 3蛋白降解。我们的发现拓宽了对ADP-核糖基转移酶家族成员抗病毒功能的理解,并提供了针对病毒ZIKV感染的潜在治疗靶点。在线版本包含补充材料,可通过10.1186/s13578-021-00628-y获得。
Zika virus (ZIKV) infection and ZIKV epidemic have been continuously spreading silently throughout the world and its associated microcephaly and other serious congenital neurological complications poses a significant global threat to public health. Type I interferon response to ZIKV infection in host cells suppresses viral replication by inducing the expression of interferon-stimulated genes (ISGs). The study aims to demonstrate the anti-ZIKV mechanism of PARP11. PARP11 knock out and overexpressing A549 cell lines were constructed to evaluate the anti-ZIKV function of PARP11. PARP11−/−, PARP12−/− and PARP11−/−PARP12−/− HEK293T cell lines were constructed to explain the synergistic effect of PARP11 and PARP12 on NS1 and NS3 protein degradation. Western blotting, immunofluorescence and immunoprecipitation assay were performed to illustrate the interaction between PARP11 and PARP12. Both mRNA and protein levels of PARP11 were induced in WT but not IFNAR1−/− cells in response to IFNα or IFNβ stimulation and ZIKV infection. ZIKV replication was suppressed in cells expressed PARP11 but was enhanced in PARP11−/− cells. PARP11 suppressed ZIKV independently on itself PARP enzyme activity. PARP11 interacted with PARP12 and promoted PARP12-mediated ZIKV NS1 and NS3 protein degradation. We identified ADP-ribosyltransferase PARP11 as an anti-ZIKV ISG and found that it cooperated with PARP12 to enhance ZIKV NS1 and NS3 protein degradation. Our findings have broadened the understanding of the anti-viral function of ADP-ribosyltransferase family members, and provided potential therapeutic targets against viral ZIKV infection. The online version contains supplementary material available at 10.1186/s13578-021-00628-y.
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