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Updated: May 3, 2026
Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
SERTAD3 induces proteasomal degradation of ZIKV capsid protein and represents a therapeutic target
Nina Sun1,2,3, Rong-Rong Zhang4, Guang-Yuan Song4,5
1Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Zika virus (ZIKV) is a mosquito-borne RNA virus that belongs to the Flaviviridae family. While flavivirus replication is known to occur in the cytoplasm, a significant portion of the viral capsid protein localizes to the nucleus during infection. However, the role of the nuclear capsid is less clear. Herein, we demonstrated SERTA domain containing 3 (SERTAD3) as an antiviral interferon stimulatory gene product had an antiviral ability to ZIKV but not JEV. Mechanistically, we found that SERTAD3 interacted with the capsid protein of ZIKV in the nucleolus and reduced capsid protein abundance through proteasomal degradation. Furthermore, an eight amino acid peptide of SERTAD3 was identified as the minimum motif that binds with ZIKV capsid protein. Remarkably, the eight amino acids synthetic peptide from SERTAD3 significantly prevented ZIKV infection in culture and pregnant mouse models. Taken together, these findings not only reveal the function of SERTAD3 in promoting proteasomal degradation of a specific viral protein but also provide a promising host-targeted therapeutic strategy against ZIKV infection.
Insights
This study identifies SERTA domain containing 3 (SERTAD3) as a host factor inhibiting Zika virus (ZIKV) replication. A small SERTAD3 peptide effectively prevents ZIKV infection, offering a potential therapeutic strategy.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Zika virus (ZIKV), a Flaviviridae family member, replicates in the cytoplasm, yet its capsid protein localizes to the nucleus.
- The function of nuclear viral capsid proteins remains largely uncharacterized.
Purpose of the Study:
- To investigate the antiviral role of SERTA domain containing 3 (SERTAD3) against ZIKV infection.
- To elucidate the mechanism by which SERTAD3 inhibits ZIKV replication.
Main Methods:
- Assessed the antiviral activity of SERTAD3 against ZIKV and Japanese encephalitis virus (JEV).
- Investigated the interaction between SERTAD3 and ZIKV capsid protein using biochemical assays.
- Determined the minimum peptide motif of SERTAD3 responsible for ZIKV capsid binding.
- Evaluated the efficacy of a synthetic SERTAD3 peptide in ZIKV-infected cell cultures and pregnant mouse models.
Main Results:
- SERTAD3 exhibited antiviral activity against ZIKV but not JEV.
- SERTAD3 interacted with ZIKV capsid protein in the nucleolus, leading to its proteasomal degradation.
- An eight-amino acid peptide of SERTAD3 was identified as the minimal binding motif.
- The synthetic peptide significantly inhibited ZIKV infection in vitro and in vivo.
Conclusions:
- SERTAD3 promotes the proteasomal degradation of ZIKV capsid protein, thus inhibiting viral replication.
- A SERTAD3-derived peptide represents a promising host-targeted therapeutic strategy for ZIKV infection.
