Identification, functional analysis, and clinical applications of defective viral genomes.

Front Microbiol

BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, Ministry of Education Key Laboratory of Infectious Diseases Research in South China, School of Public Health, Southern Medical University, Guangzhou, China.

Published: July 2025


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Article 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310628PMC
http://dx.doi.org/10.3389/fmicb.2025.1642520DOI Listing

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Identification, functional analysis, and clinical applications of defective viral genomes.

Front Microbiol

July 2025

BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, Ministry of Education Key Laboratory of Infectious Diseases Research in South China, School of Public Health, Southern Medical University, Guangzhou, China.

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.

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RNA viruses pose a significant global public health burden due to their high mutation rates, zoonotic potential, and ability to evade immune responses. A common aspect of their replication is the generation of defective interfering particles (DIPs), which contain truncated defective viral genomes (DVGs) that depend on full-length standard (STD) virus for replication. DVGs have gained recognition as they are increasingly detected in clinical samples from natural infections.

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Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, VT 05405, USA; Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA; Vaccine Testing Center, University of Vermont, Burlington, VT 05405, USA. Electronic address: jbot

Viral defective interfering particles (DIPs) were intensely studied several decades ago but research waned leaving open many critical questions. New technologies and other advances led to a resurgence in DIP studies for negative-strand RNA viruses. While DIPs have long been recognized, their exact contribution to the outcome of acute or persistent viral infections has remained elusive.

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