Journal article
A Mutation Identified in Neonatal Microcephaly Destabilizes Zika Virus NS1 Assembly in Vitro
Scientific reports, Vol.7(1), pp.42580-42580
02/15/2017
DOI: 10.1038/srep42580
PMCID: PMC5309781
PMID: 28198446
Abstract
An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1(172-352),which forms a head-to-head, symmetric dimer with a unique 14-stranded beta-ladder conserved among flaviviruses. The assembly of the beta-ladder dimer is concentration dependent. Strikingly, one pathogenic mutation T233A (NCBI accession no. KU527068), found in the brain tissue of infected fetus with neonatal microcephaly, is located at the dimer interface. Thr233, a unique residue found in ZIKV but not in other flaviviruses, organizes a central hydrogen bonding network at NS1 dimer interface. Mutation of Thr233 to Ala disrupts this elaborated interaction network, and destabilizes the NS1 dimeric assembly in vitro. In addition, our structural comparison of epitopes for protective antibody 22NS1, targeting West Nile Virus NS1, could potentially be valuable in understanding its anti-virus specificities and in the development of antibodies against ZIKV.
Details
- Title: Subtitle
- A Mutation Identified in Neonatal Microcephaly Destabilizes Zika Virus NS1 Assembly in Vitro
- Creators
- Deping Wang - Tianjin UniversityCheng Chen - Tianjin UniversityShengnan Liu - Tianjin UniversityHan Zhou - Tianjin UniversityKailin Yang - Cleveland Clinic Lerner College of MedicineQi Zhao - Yale UniversityXiaoyun Ji - Yale UniversityChen Chen - Tianjin UniversityWei Xie - Tianjin UniversityZefang Wang - Tianjin International Joint Academy of BiomedicineLi-Zhi Mi - Tianjin UniversityHaitao Yang - Tianjin International Joint Academy of Biomedicine
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7(1), pp.42580-42580
- Publisher
- NATURE PORTFOLIO
- DOI
- 10.1038/srep42580
- PMID
- 28198446
- PMCID
- PMC5309781
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Number of pages
- 10
- Grant note
- 31528006; 31470730 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) 2015CB859800; 2014CB542800 / National Key Basic Research Program of China (973 program); National Basic Research Program of China
- Language
- English
- Date published
- 02/15/2017
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984696579402771
Metrics
11 Record Views