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REVIEW ARTICLE

Defective viral genomes for antiviral therapeutics, vector control, spillover prevention, and vaccine development

Chun Hao Theo1† ,  Xi Wen Peng1† ,  I-Ching Sam1 ,  Yoke Fun Chan1*
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1 Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
†These authors contributed equally to this work.
EJMO, 025320343 https://doi.org/10.36922/EJMO025320343
Received: 4 August 2025 | Revised: 17 September 2025 | Accepted: 25 September 2025 | Published online: 24 October 2025
© 2025 by the Aurhor(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Defective viral genomes (DVGs) are altered forms of viral genomes generated during error-prone replication, particularly in RNA viruses. This review examines the current understanding of DVG biology, its mechanisms of action, and its translational potential as an antiviral agent, in vector control strategies, zoonotic disease spillover prevention, and vaccine development. DVGs modulate virus-host interactions by interfering with the replication of full-length viruses and/or activating innate immune responses. Both naturally occurring and synthetic DVGs could suppress viral loads, reduce disease severity, and enhance the efficacy of inactivated and live attenuated vaccines. DVG-derived particles, such as defective interfering particles and therapeutic interfering particles, have shown broad-spectrum antiviral activity against numerous viruses in vitro and in vivo. By reducing viral replication in both insect and animal hosts, DVGs may block the vector transmission cycle and prevent spillover between species, thus playing a key role in controlling arthropod-borne viruses and zoonotic diseases. However, DVGs could contribute to viral persistence, which may hamper their clinical application. Additional challenges include standardizing DVGs production, understanding their effects on adaptive immunity, and ensuring their safety profile as vaccines or vaccine adjuvants.

Graphical abstract
Keywords
Defective viral genomes
Defective interfering particles
Therapeutic interfering particles
One Health
Antiviral
Vaccine
Funding
Chun Hao Theo is supported by the Universiti Malaya Faculty of Medicine Postgraduate Scholarship Fund. This study was funded by Universiti Malaya (project code MG001-2024).
Conflict of interest
The authors declare they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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