AUTHOR=Yan Xiaowei , Pan Yitong , Li Peiying , Zhu Li , Yu Jianhai , Shen Chenguang , Zhang Bao , Zhao Wei 

TITLE=Identification, functional analysis, and clinical applications of defective viral genomes

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1642520

DOI=10.3389/fmicb.2025.1642520

ISSN=1664-302X

ABSTRACT=Defective viral genomes (DVGs) are fragments derived from defective interfering particles (DIPs) that form during viral replication. They play important roles by interfering with complete virus replication and regulating host immune responses. Advances in high-throughput sequencing (HTS) and bioinformatic technology have significantly improved the ability to identify DIPs and DVGs. Their heterogeneity and dynamic formation mechanisms have been analyzed using long-read sequencing technologies. Both DIPs and DVGs inhibit wild-type viral proliferation by competing for viral replication resources and activating innate immune pathways such as those of retinoic acid-inducible gene 1 and mitochondrial antiviral signaling protein. This might influence infection outcomes by regulating inflammatory cytokine storms. The clinical application of DIPs and DVGs in their natural attenuated virus forms has been investigated in terms of novel vaccine design and antiviral therapy. This report systematically reviews cutting-edge detection techniques, molecular mechanisms, and translational medicine advances of DIPs and DVGs and provides a theoretical basis for developing broad-spectrum antiviral strategies based on DIPs.