Defective viral genomes: advances in understanding their generation, function, and impact on infection outcomes

Abstract

Defective viral genomes (DVGs) are truncated derivatives of their parental viral genomes generated during an aberrant round of viral genomic replication. Distinct classes of DVGs have been identified in most families of both positive- and negative-sense RNA viruses. Importantly, DVGs have been detected in clinical samples from virally infected individuals and an emerging body of association studies implicates DVGs in shaping the severity of disease caused by viral infections in humans. Consequently, there is growing interest in understanding the molecular mechanisms of de novo DVG generation, how DVGs interact with the innate immune system, and harnessing DVGs as novel therapeutics and vaccine adjuvants to attenuate viral pathogenesis. This minireview focuses on single-stranded RNA viruses (excluding retroviridae), and summarizes the current knowledge of DVG generation, the functions and diversity of DVG species, the roles DVGs play in influencing disease progression, and their application as antivirals and vaccine adjuvants.

Influenza A defective viral genomes and non-infectious particles are increased by host PI3K inhibition via anti-cancer drug alpelisib

“…RNA virus infections frequently produce defective viral genomes, which can influence the course of infection through interactions such as complementation and interference (Dimmock, 2014). Non-clinical studies have extensively associated defective viral genome accumulation with reduced disease severity, while fewer but notable clinical studies have demonstrated this trend in Influenza A (Vasilijevic, 2017) and Respiratory Syncytial Virus (Felt, 2021) infections (Brennan, 2024). Consequently, defective viral genomes have become a recent focus of intense pre-clinical research (Smith, 2016; Meng, 2017; Wasik, 2018; Zhao, 2018; Bdier, 2019; Yamagata, 2019; Tapia, 2019; Harding, 2019), with their antiviral potential holding substantial implications for clinical applications and pandemic preparedness.…”