Non-Structural Protein 5 of Zika Virus Interacts with p53 in Human Neural Progenitor Cells and Induces p53-Mediated Apoptosis  

作　　者：Ping Li Hualian Jiang Hong Peng Weijie Zeng Yongheng Zhong Miao He Luyang Xie Junhai Chen Deyin Guo Junyu Wu Chun-Mei Li 

机构地区：[1]MOE Key Laboratory of Tropical Disease Control,Centre for Infection and Immunity Study(CIIS),School of Medicine,Sun Yat-Sen University,Shenzhen,518197,China

出　　处：《Virologica Sinica》2021年第6期1411-1420,共10页中国病毒学（英文版）

基　　金：The work is supported by the National Natural Science Foundation of China[NSFC Grant#81620108020 and#32041002,to D.G.,Grant#31800151,to J.W.];Guangdong Zhujiang Talents Program(to D.G.);Shenzhen Science and Technology Program[Grant#KQTD20180411143323605 and#JSGG20200225150431472 to D.G.];National Ten-thousand Talents Program(to D.G.);Guangdong Province “Pearl River Talent Plan” Innovation and Entrepreneurship Team Project(Grant #2019ZT08Y464 to Li,C.M)。

摘　　要：Zika virus(ZIKV) infection could disrupt neurogenesis and cause microcephaly in neonates by targeting neural progenitor cells(NPCs). The tumor suppressor p53-mediated cell cycle arrest and apoptotic cell death have been suggested to be activated upon ZIKV infection, yet the detailed mechanism is not well understood. In the present study, we investigated the effects of ZIKV-encoded proteins in the activation of p53 signaling pathway and found that, among the ten viral proteins,the nonstructural protein 5(NS5) of ZIKV most significantly activated the transcription of p53 target genes. Using the immunoprecipitation-coupled mass spectrometry approach, we identified that ZIKV-NS5 interacted with p53 protein. The NS5-p53 interaction was further confirmed by co-immunoprecipitation and GST pull-down assays. In addition, the MTase domain of NS5 and the C-terminal domain of p53 were mapped to be responsible for the interaction between these two proteins. We further showed that ZIKV-NS5 was colocalized with p53 and increased its protein level in the nuclei and able to prolong the half-life of p53. Furthermore, lentivirus-mediated expression of ZIKV-NS5 in hNPCs led to an apparent cell death phenotype. ZIKV-NS5 promoted the cleavage of PARP1 and significantly increased the cell apoptosis of h NPCs.Taken together, these findings revealed that ZIKV-NS5 is a previously undiscovered regulator of p53-mediated apoptosis in hNPCs, which may contribute to the ZIKV-caused abnormal neurodevelopment.

关 键 词：Zika virus(ZIKV) Nonstructural protein 5(NS5) P53 APOPTOSIS Human neural progenitor cells(hNPCs) 

分 类 号：R373[医药卫生—病原生物学]