An Integrative Analysis Reveals a Central Role of P53 Activation via MDM2 in Zika Virus Infection Induced Cell Death

• Main Authors: Yue Teng, Shufeng Liu, Xiaocan Guo, Shuxia Liu, Yuan Jin, Tongtong He, Dehua Bi, Pei Zhang, Baihan Lin, Xiaoping An, Dan Feng, Zhiqiang Mi, Yigang Tong
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-07-01
• Series: Frontiers in Cellular and Infection Microbiology
• Subjects: Zika virus; microcephaly; capsid protein; P53; MDM2; cell death
• Online Access: http://journal.frontiersin.org/article/10.3389/fcimb.2017.00327/full

Zika virus (ZIKV) infection is an emerging global threat that is suspected to be associated with fetal microcephaly. However, the molecular mechanisms underlying ZIKV disease pathogenesis in humans remain elusive. Here, we investigated the human protein interaction network associated with ZIKV infection using a systemic virology approach, and reconstructed the transcriptional regulatory network to analyze the mechanisms underlying ZIKV-elicited microcephaly pathogenesis. The bioinformatics findings in this study show that P53 is the hub of the genetic regulatory network for ZIKV-related and microcephaly-associated proteins. Importantly, these results imply that the ZIKV capsid protein interacts with mouse double-minute-2 homolog (MDM2), which is involved in the P53-mediated apoptosis pathway, activating the death of infected neural cells. We also found that synthetic mimics of the ZIKV capsid protein induced cell death in vitro and in vivo. This study provides important insight into the relationship between ZIKV infection and brain diseases.