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Updated: Jun 14, 2026
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Rescue and Characterization of Recombinant Virus from a New World Zika Virus Infectious Clone
Published on: June 7, 2017
10.1K
Manipulating Zika virus RNA tertiary structure for developing tissue-specific attenuated vaccines.
Xiang Chen1, Meng-Li Cheng2, Xing-Yao Huang1
1State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, 100071, Beijing, China.
EMBO Molecular Medicine
|September 9, 2025
Summary
This study shows that altering Zika virus RNA structures to block host protein binding creates a safe and effective live attenuated vaccine (LAV). This new vaccine platform offers protection against emerging viruses.
Area of Science:
- Virology
- Vaccinology
- Molecular Biology
Background:
- Live attenuated vaccines (LAVs) are traditionally developed via passaging or genetic engineering.
- Viral RNA structures' roles in host protein binding are known, but their use in LAV design is underexplored.
Purpose of the Study:
- To investigate the potential of targeting viral RNA structures for live attenuated vaccine (LAV) development.
- To engineer Zika virus (ZIKV) mutants with impaired binding to the host protein Musashi-1 (MSI1) for attenuation.
Main Methods:
- Zika virus (ZIKV) was engineered to disrupt a specific viral RNA element binding to Musashi-1 (MSI1).
- Tissue-specific attenuation and vertical transmission were assessed in multiple animal models.
- Immunogenicity and protective efficacy against ZIKV challenge were evaluated in mice and non-human primates.
Main Results:
- MSI1-binding-deficient ZIKV mutants (MBD) showed tissue-specific attenuation, restricted in ZIKV-vulnerable tissues but not MSI1-deficient tissues.
- Engineered MBD ZIKV exhibited significantly reduced vertical transmission in mice.
- A single immunization with MBD ZIKV elicited robust immune responses and provided protection against ZIKV challenge in mice and non-human primates.
Conclusions:
- Targeting viral RNA structures that interact with host proteins is a viable strategy for developing next-generation LAVs.
- This approach offers a powerful platform for creating attenuated vaccines against emerging viruses like ZIKV.
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