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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Momordica anti-HIV protein MAP30 abrogates the Epstein-Barr virus nuclear antigen 1 dependent functions in host cells
Wei-Hang Huang1,2, Wen-Min Su3, Chung-Wei Wang3
1Department of Clinical Pathology Department of Hematology & Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 97002 Taiwan.
Abstract:
Originally extracted from Momordica charantia seeds, the antiviral and anti-tumor activities of Momordica anti-HIV protein MAP30 have become well known. Although MAP30 has been reported to possess antiviral activity against several human viruses, the current understanding of the MAP30-mediated antiviral response is mainly derived from the previous research work on anti-HIV herbal medicines; the mechanistic insight of its effects on other viruses remains largely unknown. In this study, we showed that both ectopically expressed and purified recombinant MAP30 (rMAP30) impeded Epstein-Barr virus Nuclear Antigen 1 (EBNA1)-mediated transcription from the viral latent replication origin. Mechanistically, in vivo and in vitro studies revealed that MAP30 caused EBNA1 to dissociate from the cognate binding sites, which disrupted downstream EBNA1-dependent viral epigenome accumulation and cell maintenance of Epstein-Barr virus (EBV)-associated neoplastic cells. Finally, mutational analysis indicated that the N-terminal ricin A homologous domain shared by ricin-like proteins was implicated in the anti-EBV response. Our study provides evidence to support that MAP30 has a unique property to combat EBV latent infection, suggesting a potential to develop this herbal protein to be an alternative medicine for EBV associated diseases.
Insights
Momordica anti-HIV protein MAP30 inhibits Epstein-Barr virus (EBV) replication by disrupting viral protein EBNA1 binding. This discovery suggests MAP30 as a potential treatment for EBV-associated diseases.
Area of Science:
- Biochemistry
- Virology
- Molecular Biology
Background:
- Momordica anti-HIV protein MAP30, derived from Momordica charantia seeds, is known for antiviral and anti-tumor activities.
- Previous research on MAP30's antiviral effects primarily focused on HIV, with limited understanding of its mechanisms against other viruses.
Purpose of the Study:
- To investigate the antiviral activity of MAP30 against Epstein-Barr virus (EBV).
- To elucidate the molecular mechanisms underlying MAP30's effects on EBV latent replication.
Main Methods:
- Ectopic expression and purification of recombinant MAP30 (rMAP30).
- Assays to assess EBNA1-mediated transcription from the viral latent replication origin.
- In vivo and in vitro studies to analyze protein-DNA interactions and epigenome modifications.
- Mutational analysis of MAP30's functional domains.
Main Results:
- Both expressed and purified MAP30 inhibited EBNA1-mediated transcription from the EBV latent replication origin.
- MAP30 caused EBNA1 to dissociate from its binding sites, disrupting viral epigenome accumulation.
- The N-terminal ricin A homologous domain of MAP30 was identified as crucial for its anti-EBV activity.
Conclusions:
- MAP30 exhibits a unique ability to combat EBV latent infection.
- MAP30 disrupts EBV replication by interfering with EBNA1 function.
- MAP30 holds potential as an alternative therapeutic agent for EBV-associated diseases.
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