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

Abstract

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.

• 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
• Journal: Frontiers in cellular and infection microbiology (Front Cell Infect Microbiol) Vol. 7 Pg. 327 ( 2017) ISSN: 2235-2988 [Electronic] Switzerland
• PMID: 28775961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Capsid Proteins
• Tumor Suppressor Protein p53
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2

Topics

• Animals
• Brain (pathology)
• Capsid Proteins (metabolism)
• Cell Death
• Cell Line
• Computational Biology
• Disease Models, Animal
• Gene Regulatory Networks
• Histocytochemistry
• Host-Pathogen Interactions
• Humans
• Immunohistochemistry
• Mice, Inbred BALB C
• Protein Interaction Maps
• Proto-Oncogene Proteins c-mdm2 (metabolism)
• Tumor Suppressor Protein p53 (metabolism)
• Zika Virus (growth & development)
• Zika Virus Infection (pathology)