{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:46:44Z","timestamp":1792136804907,"version":"4.4.0"},"reference-count":145,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fmicb.2025.1642520","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T05:24:58Z","timestamp":1752729898000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification, functional analysis, and clinical applications of defective viral genomes"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaowei","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhai","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2971","DOI":"10.1080\/07391102.2020.1758790","article-title":"Moroccan medicinal plants as inhibitors against SARS-CoV-2 main protease: computational investigations","volume":"39","author":"Aanouz","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1128\/JVI.00250-21","article-title":"In vivo generation of BK and JC polyomavirus defective viral genomes in human urine samples associated with higher viral loads","volume":"95","author":"Addetia","year":"2021","journal-title":"J. Virol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e0295921","DOI":"10.1128\/mBio.02959-21","article-title":"Influenza a virus defective viral genomes are inefficiently packaged into Virions relative to wild-type genomic RNAs","volume":"12","author":"Alnaji","year":"2021","journal-title":"MBio"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1128\/jvi.59.2.472-478.1986","article-title":"Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis","volume":"59","author":"Baczko","year":"1986","journal-title":"J. Virol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41587-020-0507-2","article-title":"Viral contamination in biologic manufacture and implications for emerging therapies","volume":"38","author":"Barone","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1093\/infdis\/150.1.98","article-title":"Modulation of Semliki Forest virus-induced infection of mice by defective-interfering virus","volume":"150","author":"Barrett","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e0212757","DOI":"10.1371\/journal.pone.0212757","article-title":"A system for production of defective interfering particles in the absence of infectious influenza a virus","volume":"14","author":"Bdeir","year":"2019","journal-title":"PLoS One"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1261\/rna.066910.118","article-title":"DI-tector: defective interfering viral genomes' detector for next-generation sequencing data","volume":"24","author":"Beauclair","year":"2018","journal-title":"RNA"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/1045-1056(90)90039-3","article-title":"Wide occurrence of measles virus subgenomic RNAs in attenuated live-virus vaccines","volume":"18","author":"Bellocq","year":"1990","journal-title":"Biologicals"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"101174","DOI":"10.1016\/j.patter.2025.101174","article-title":"SplitFusion enables ultrasensitive gene fusion detection and reveals fusion variant-associated tumor heterogeneity","volume":"6","author":"Bian","year":"2025","journal-title":"Patterns"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e0216944","DOI":"10.1371\/journal.pone.0216944","article-title":"Identification and quantification of defective virus genomes in high throughput sequencing data using DVG-profiler, a novel post-sequence alignment processing algorithm","volume":"14","author":"Bosma","year":"2019","journal-title":"PLoS One"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e0069224","DOI":"10.1128\/mbio.00692-24","article-title":"Defective viral genomes: advances in understanding their generation, function, and impact on infection outcomes","volume":"15","author":"Brennan","year":"2024","journal-title":"MBio"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2859","DOI":"10.1128\/jvi.62.8.2859-2866.1988","article-title":"Generation of measles virus defective interfering particles and their presence in a preparation of attenuated live-virus vaccine","volume":"62","author":"Calain","year":"1988","journal-title":"J. Virol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1006\/viro.1995.1464","article-title":"Functional characterisation of the genomic and antigenomic promoters of Sendai virus","volume":"212","author":"Calain","year":"1995","journal-title":"Virology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41586-021-04385-3","article-title":"Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies","volume":"602","author":"Cao","year":"2022","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"384","DOI":"10.3390\/genes12030384","article-title":"iVar, an interpretation-oriented tool to manage the update and revision of variant annotation and classification","volume":"12","author":"Castellano","year":"2021","journal-title":"Genes"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/0042-6822(91)90160-D","article-title":"Protection of chickens from lethal influenza virus infection by influenza a\/chicken\/Pennsylvania\/1\/83 virus: characterization of the protective effect","volume":"183","author":"Chambers","year":"1991","journal-title":"Virology"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e2204624119","DOI":"10.1073\/pnas.2204624119","article-title":"A single-administration therapeutic interfering particle reduces SARS-CoV-2 viral shedding and pathogenesis in hamsters","volume":"119","author":"Chaturvedi","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"6022","DOI":"10.1016\/j.cell.2021.11.004","article-title":"Identification of a therapeutic interfering particle-a single-dose SARS-CoV-2 antiviral intervention with a high barrier to resistance","volume":"184","author":"Chaturvedi","year":"2021","journal-title":"Cell"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1128\/jvi.36.3.847-859.1980","article-title":"Defective interfering influenza viruses and host cells: establishment and maintenance of persistent influenza virus infection in MDBK and HeLa cells","volume":"36","author":"De","year":"1980","journal-title":"J. Virol."},{"key":"ref21","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1099\/0022-1317-67-5-839","article-title":"Protection of mice from lethal influenza: evidence that defective interfering virus modulates the immune response and not virus multiplication","volume":"67","author":"Dimmock","year":"1986","journal-title":"J. Gen. Virol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"5217","DOI":"10.1128\/JVI.03193-13","article-title":"Defective interfering influenza virus RNAs: time to reevaluate their clinical potential as broad-spectrum antivirals?","volume":"88","author":"Dimmock","year":"2014","journal-title":"J. Virol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1073\/pnas.70.7.2105","article-title":"Prophylaxis and immunization in mice by use of virus-free defective T particles to protect against intracerebral infection by vesicular stomatitis virus","volume":"70","author":"Doyle","year":"1973","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/s41586-023-06609-0","article-title":"Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir","volume":"622","author":"Duan","year":"2023","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1006\/viro.2000.0502","article-title":"Approximately 150 nucleotides from the 5\u2032 end of an influenza a segment 1 defective virion RNA are needed for genome stability during passage of defective virus in infected cells","volume":"275","author":"Duhaut","year":"2000","journal-title":"Virology"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine Storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/s41564-021-00882-3","article-title":"Detection of respiratory syncytial virus defective genomes in nasal secretions is associated with distinct clinical outcomes","volume":"6","author":"Felt","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"547","DOI":"10.2217\/fvl.15.5","article-title":"Cytokines and viral hemorrhagic fever: potential for therapeutic intervention","volume":"10","author":"Findlay","year":"2015","journal-title":"Future Virol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"4039","DOI":"10.1016\/j.vaccine.2018.05.100","article-title":"Virus-derived immunostimulatory RNA induces type I IFN-dependent antibodies and T-cell responses during vaccination","volume":"36","author":"Fisher","year":"2018","journal-title":"Vaccine"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3664","DOI":"10.1002\/rmv.2231","article-title":"Neutralising antibody escape of SARS-CoV-2 spike protein: risk assessment for antibody-based Covid-19 therapeutics and vaccines","volume":"31","author":"Focosi","year":"2021","journal-title":"Rev. Med. Virol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1099\/0022-1317-48-1-63","article-title":"Interferon induction by viruses. IV. Sindbis virus: early passage defective-interfering particles induce interferon","volume":"48","author":"Fuller","year":"1980","journal-title":"J. Gen. Virol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1016\/j.cell.2021.03.013","article-title":"Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity","volume":"184","author":"Garcia-Beltran","year":"2021","journal-title":"Cell"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e3257","DOI":"10.1371\/journal.pntd.0003257","article-title":"The global one health paradigm: challenges and opportunities for tackling infectious diseases at the human, animal, and environment interface in low-resource settings","volume":"8","author":"Gebreyes","year":"2014","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1146\/annurev-virology-092818-015652","article-title":"The impact of defective viruses on infection and immunity","volume":"6","author":"Genoyer","year":"2019","journal-title":"Annu. Rev. Virol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"9125398","DOI":"10.1155\/2024\/9125398","article-title":"Challenges in emerging vaccines and future promising candidates against SARS-CoV-2 variants","volume":"2024","author":"Ghildiyal","year":"2024","journal-title":"J Immunol Res"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/0042-6822(89)90375-9","article-title":"Vesicular stomatitis virus and its defective interfering particles exhibit in vitro transcriptional and replicative competition for purified L-NS polymerase molecules","volume":"170","author":"Giachetti","year":"1989","journal-title":"Virology"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1038\/s42003-022-04058-5","article-title":"Evolution of naturally arising SARS-CoV-2 defective interfering particles","volume":"5","author":"Girgis","year":"2022","journal-title":"Commun. Biol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3390\/v9100269","article-title":"Live attenuated influenza vaccine contains substantial and unexpected amounts of defective viral genomic RNA","volume":"9","author":"Gould","year":"2017","journal-title":"Viruses"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41541-018-0049-5","article-title":"Baseline mapping of Lassa fever virology, epidemiology and vaccine research and development","volume":"3","author":"Hallam","year":"2018","journal-title":"NPJ Vaccines"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s12915-021-01020-5","article-title":"Cell culture-based production and in vivo characterization of purely clonal defective interfering influenza virus particles","volume":"19","author":"Hein","year":"2021","journal-title":"BMC Biol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s00253-020-11029-5","article-title":"OP7, a novel influenza a virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential","volume":"105","author":"Hein","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1126\/science.1179555","article-title":"CRISPR\/Cas, the immune system of bacteria and archaea","volume":"327","author":"Horvath","year":"2010","journal-title":"Science"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12985-025-02654-5","article-title":"Diverse effects of coronavirus-defective viral genomes on the synthesis of IFN\u03b2 and ISG15 mRNAs and coronavirus replication","volume":"22","author":"Hsu","year":"2025","journal-title":"Virol. J."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/226325a0","article-title":"Defective viral particles and viral disease processes","volume":"226","author":"Huang","year":"1970","journal-title":"Nature"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/0042-6822(66)90092-4","article-title":"Defective T particles of vesicular stomatitis virus. I. preparation, morphology, and some biologic properties","volume":"30","author":"Huang","year":"1966","journal-title":"Virology"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"553274","DOI":"10.3389\/fmicb.2020.553274","article-title":"Defective viral particles produced in mast cells can effectively fight against lethal influenza a virus","volume":"11","author":"Huo","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0071-8","article-title":"Single-cell RNA sequencing technologies and bioinformatics pipelines","volume":"50","author":"Hwang","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/s41586-022-05514-2","article-title":"Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir","volume":"613","author":"Iketani","year":"2023","journal-title":"Nature"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1016\/j.ymthe.2025.03.055","article-title":"Next-generation replication-defective HSV vectors for delivery of large DNA payloads","volume":"33","author":"Ingusci","year":"2025","journal-title":"Mol. Ther."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41572-020-0147-3","article-title":"Ebola virus disease","volume":"6","author":"Jacob","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1370564","DOI":"10.3389\/fimmu.2024.1370564","article-title":"Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in quadrivalent influenza vaccine vaccinated mice","volume":"15","author":"Jangra","year":"2024","journal-title":"Front. Immunol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"5644","DOI":"10.1038\/s41467-024-49992-6","article-title":"Low-input PacBio sequencing generates high-quality individual fly genomes and characterizes mutational processes","volume":"15","author":"Jia","year":"2024","journal-title":"Nat. Commun."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3390\/v13020214","article-title":"Lassa virus vaccine candidate ML29 generates truncated viral RNAs which contribute to interfering activity and attenuation","volume":"13","author":"Johnson","year":"2021","journal-title":"Viruses"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1099\/0022-1317-56-1-175","article-title":"The characteristics required for a Sendai virus preparation to induce high levels of interferon in human lymphoblastoid cells","volume":"56","author":"Johnston","year":"1981","journal-title":"J. Gen. Virol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/0042-6822(75)90452-3","article-title":"Characterization of rabies viruses recovered from persistently infected BHK cells","volume":"67","author":"Kawai","year":"1975","journal-title":"Virology"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s41565-021-00866-8","article-title":"Nanotechnology approaches for global infectious diseases","volume":"16","author":"Kirtane","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/0092-8674(76)90223-3","article-title":"Isolation and characterization of Sendai virus DI-RNAs","volume":"8","author":"Kolakofsky","year":"1976","journal-title":"Cell"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/0042-6822(79)90263-0","article-title":"Studies on the generation and amplification of Sendai virus defective-interfering genomes","volume":"93","author":"Kolakofsky","year":"1979","journal-title":"Virology"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1128\/JVI.01786-18","article-title":"A novel type of influenza a virus-derived defective interfering particle with nucleotide substitutions in its genome","volume":"93","author":"Kupke","year":"2019","journal-title":"J. Virol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/0092-8674(81)90298-1","article-title":"The origins of defective interfering particles of the negative-strand RNA viruses","volume":"26","author":"Lazzarini","year":"1981","journal-title":"Cell"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/s41434-024-00500-x","article-title":"Non-replicative herpes simplex virus genomic and amplicon vectors for gene therapy - an update","volume":"32","author":"Le Hars","year":"2025","journal-title":"Gene Ther."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"e1009110","DOI":"10.1371\/journal.ppat.1009110","article-title":"Defective viral genomes from chikungunya virus are broad-spectrum antivirals and prevent virus dissemination in mosquitoes","volume":"17","author":"Levi","year":"2021","journal-title":"PLoS Pathog."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.virol.2014.08.013","article-title":"Sub-genomic RNA of defective interfering (D.I.) dengue viral particles is replicated in the same manner as full length genomes","volume":"468","author":"Li","year":"2014","journal-title":"Virology"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"104761","DOI":"10.1016\/j.phrs.2020.104761","article-title":"Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)","volume":"156","author":"Li","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s42003-021-02064-7","article-title":"Dengue virus-free defective interfering particles have potent and broad anti-dengue virus activity","volume":"4","author":"Li","year":"2021","journal-title":"Commun. Biol."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"199274","DOI":"10.1016\/j.virusres.2023.199274","article-title":"5\u2032 copyback defective viral genomes are major component in clinical and non-clinical influenza samples","volume":"339","author":"Li","year":"2024","journal-title":"Virus Res."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"e98422","DOI":"10.1371\/journal.pone.0098422","article-title":"The 3\u2032-terminal 55 nucleotides of bovine coronavirus defective interfering RNA harbor cis-acting elements required for both negative- and positive-strand RNA synthesis","volume":"9","author":"Liao","year":"2014","journal-title":"PLoS One"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"e0394922","DOI":"10.1128\/spectrum.03949-22","article-title":"Defective interfering particles with broad-acting antiviral activity for dengue, Zika, yellow fever, respiratory syncytial and SARS-CoV-2 virus infection","volume":"10","author":"Lin","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"8720","DOI":"10.1128\/JVI.00707-14","article-title":"Defective viral genomes: critical danger signals of viral infections","volume":"88","author":"L\u00f3pez","year":"2014","journal-title":"J. Virol."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"e0008821","DOI":"10.1128\/JVI.00088-21","article-title":"Defective Epstein-Barr virus genomes and atypical viral gene expression in B-cell lines derived from multiple myeloma patients","volume":"95","author":"Lu","year":"2021","journal-title":"J. Virol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"493","DOI":"10.2217\/fvl-2018-0021","article-title":"Defective (interfering) viral genomes re-explored: impact on antiviral immunity and virus persistence","volume":"13","author":"Manzoni","year":"2018","journal-title":"Future Virol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/0042-6822(89)90637-5","article-title":"Interferon induction by viruses. XIX. Vesicular stomatitis virus--New Jersey: high multiplicity passages generate interferon-inducing, defective-interfering particles","volume":"171","author":"Marcus","year":"1989","journal-title":"Virology"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1128\/CMR.00035-09","article-title":"Dengue virus pathogenesis: an integrated view","volume":"22","author":"Martina","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41592-022-01730-w","article-title":"Method of the year: long-read sequencing","volume":"20","author":"Marx","year":"2023","journal-title":"Nat. Methods"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.cnur.2019.02.006","article-title":"Emerging infectious diseases","volume":"54","author":"McArthur","year":"2019","journal-title":"Nurs. Clin. North Am."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/0042-6822(74)90352-3","article-title":"Defective interfering particles from poliovirus vaccine and vaccine reference strains","volume":"60","author":"McLaren","year":"1974","journal-title":"Virology"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"5713","DOI":"10.1016\/j.vaccine.2013.09.040","article-title":"Highly immunostimulatory RNA derived from a Sendai virus defective viral genome","volume":"31","author":"Mercado-L\u00f3pez","year":"2013","journal-title":"Vaccine"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"e1002015","DOI":"10.1371\/journal.pcbi.1002015","article-title":"Autonomous targeting of infectious superspreaders using engineered transmissible therapies","volume":"7","author":"Metzger","year":"2011","journal-title":"PLoS Comput. Biol."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"5077","DOI":"10.1038\/s41598-022-09035-w","article-title":"The ViReflow pipeline enables user friendly large scale viral consensus genome reconstruction","volume":"12","author":"Moshiri","year":"2022","journal-title":"Sci. Rep."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1093\/bioinformatics\/btae651","article-title":"Quantifying defective and wild-type viruses from high-throughput RNA sequencing","volume":"40","author":"Mu\u00f1oz-S\u00e1nchez","year":"2024","journal-title":"Bioinformatics"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1136\/bmjmilitary-2020-001415","article-title":"Communicable diseases in humanitarian operations and disasters","volume":"168","author":"Murphy","year":"2022","journal-title":"BMJ Mil. Health."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"vbaf115","DOI":"10.1093\/bioadv\/vbaf115","article-title":"Bonoboflow: viral genome assembly and haplotype reconstruction from nanopore reads","volume":"5","author":"Ndekezi","year":"2025","journal-title":"Bioinform. Adv."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/0025-5564(94)00021-Q","article-title":"Modeling defective interfering virus therapy for AIDS: conditions for DIV survival","volume":"125","author":"Nelson","year":"1995","journal-title":"Math. Biosci."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"2775","DOI":"10.1093\/nar\/12.6.2775","article-title":"Structure and origin of a novel class of defective interfering particle of vesicular stomatitis virus","volume":"12","author":"Nichol","year":"1984","journal-title":"Nucleic Acids Res."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/v14051114","article-title":"DVGfinder: a metasearch tool for identifying defective viral genomes in RNA-Seq data","volume":"14","author":"Olmo-Uceda","year":"2022","journal-title":"Viruses"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"895","DOI":"10.3390\/v1030895","article-title":"Defective interfering RNAs: foes of viruses and friends of virologists","volume":"1","author":"Pathak","year":"2009","journal-title":"Viruses"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"872","DOI":"10.3390\/v15091872","article-title":"Broad-spectrum antiviral activity of influenza a defective interfering particles against respiratory syncytial, yellow fever, and Zika virus replication in vitro","volume":"15","author":"Pelz","year":"2023","journal-title":"Viruses"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"e0117421","DOI":"10.1128\/JVI.01174-21","article-title":"Semi-continuous propagation of influenza a virus and its defective interfering particles: analyzing the dynamic competition to select candidates for antiviral therapy","volume":"95","author":"Pelz","year":"2021","journal-title":"J. Virol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e0117822","DOI":"10.1128\/jvi.01178-22","article-title":"Levels of influenza a virus defective viral genomes determine pathogenesis in the BALB\/c mouse model","volume":"96","author":"Penn","year":"2022","journal-title":"J. Virol."},{"key":"ref90","first-page":"151","article-title":"Origin and replication of defective interfering particles","volume":"93","author":"Perrault","year":"1981","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1099\/0022-1317-38-1-35","article-title":"Inverted complementary terminal sequences in single-stranded RNAs and snap-back RNAs from vesicular stomatitis defective interfering particles","volume":"38","author":"Perrault","year":"1978","journal-title":"J. Gen. Virol."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"6191","DOI":"10.1073\/pnas.76.12.6191","article-title":"Internal genome deletions in two distinct classes of defective interfering particles of vesicular stomatitis virus","volume":"76","author":"Perrault","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41586-021-03777-9","article-title":"Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization","volume":"596","author":"Planas","year":"2021","journal-title":"Nature"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"2446","DOI":"10.1128\/JVI.02921-15","article-title":"Low-Fidelity polymerases of alphaviruses recombine at higher rates to overproduce defective interfering particles","volume":"90","author":"Poirier","year":"2015","journal-title":"J. Virol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1128\/jvi.8.4.388-394.1971","article-title":"Homologous interference by incomplete Sendai virus particles: changes in virus-specific ribonucleic acid synthesis","volume":"8","author":"Portner","year":"1971","journal-title":"J. Virol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1093\/infdis\/140.3.305","article-title":"The influence of defective-interfering particles of the PR-8 strain of influenza a virus on the pathogenesis of pulmonary infection in mice","volume":"140","author":"Rabinowitz","year":"1979","journal-title":"J. Infect. Dis."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"756","DOI":"10.3390\/cells10071756","article-title":"Antiviral activity of influenza a virus defective interfering particles against SARS-CoV-2 replication in vitro through stimulation of innate immunity","volume":"10","author":"Rand","year":"2021","journal-title":"Cells"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1128\/jvi.41.1.210-221.1982","article-title":"Interference among defective interfering particles of vesicular stomatitis virus","volume":"41","author":"Rao","year":"1982","journal-title":"J. Virol."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1128\/jvi.45.2.659-664.1983","article-title":"Genomic and copy-back 3\u2032 termini in Sendai virus defective interfering RNA species","volume":"45","author":"Re","year":"1983","journal-title":"J. Virol."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1038\/s41591-022-01851-x","article-title":"Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial","volume":"28","author":"Reijers","year":"2022","journal-title":"Nat. Med."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1038\/s41467-021-22341-7","article-title":"Defective viral genomes as therapeutic interfering particles against flavivirus infection in mammalian and mosquito hosts","volume":"12","author":"Rezelj","year":"2021","journal-title":"Nat. Commun."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.coviro.2018.07.014","article-title":"The defective component of viral populations","volume":"33","author":"Rezelj","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1093\/bioinformatics\/btac830","article-title":"Igv.Js: an embeddable JavaScript implementation of the integrative genomics viewer (IGV)","volume":"39","author":"Robinson","year":"2023","journal-title":"Bioinformatics"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"e11","DOI":"10.1093\/nar\/gkt916","article-title":"Discovery of functional genomic motifs in viruses with ViReMa-a virus recombination mapper-for analysis of next-generation sequencing data","volume":"42","author":"Routh","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/0042-6822(81)90287-7","article-title":"Establishment of Sendai virus persistent infection: biochemical analysis of the early phase of a standard plus defective interfering virus infection of BHK cells","volume":"112","author":"Roux","year":"1981","journal-title":"Virology"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1128\/jvi.24.2.580-589.1977","article-title":"Persistent infection of cultured mammalian cells by Japanese encephalitis virus","volume":"24","author":"Schmaljohn","year":"1977","journal-title":"J. Virol."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/s41592-018-0001-7","article-title":"Accurate detection of complex structural variations using single-molecule sequencing","volume":"15","author":"Sedlazeck","year":"2018","journal-title":"Nat. Methods"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/0042-6822(78)90422-1","article-title":"Persistent infection. I interferon-inducing defective-interfering particles as mediators of cell sparing: possible role in persistent infection by vesicular stomatitis virus","volume":"85","author":"Sekellick","year":"1978","journal-title":"Virology"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21775\/cimb.027.001","article-title":"Status and prospects of next generation sequencing Technologies in Crop Plants","volume":"27","author":"Sharma","year":"2018","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1099\/jgv.0.001018","article-title":"Identification and characterization of viral defective RNA genomes in influenza B virus","volume":"99","author":"Sheng","year":"2018","journal-title":"J. Gen. Virol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"e0095523","DOI":"10.1128\/jvi.00955-23","article-title":"Shared sequence characteristics identified in non-canonical rearrangements of HSV-1 genomes","volume":"97","author":"Shitrit","year":"2023","journal-title":"J. Virol."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"e59","DOI":"10.1002\/cpmb.59","article-title":"Overview of next-generation sequencing technologies","volume":"122","author":"Slatko","year":"2018","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/gigascience\/giad009","article-title":"ViReMa: a virus recombination mapper of next-generation sequencing data characterizes diverse recombinant viral nucleic acids","volume":"12","author":"Sotcheff","year":"2023","journal-title":"Gigascience"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"104293","DOI":"10.1016\/j.isci.2022.104293","article-title":"Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication","volume":"25","author":"Stegmann","year":"2022","journal-title":"iScience"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"12227","DOI":"10.1128\/JVI.01300-07","article-title":"Activation of the beta interferon promoter by unnatural Sendai virus infection requires RIG-I and is inhibited by viral C proteins","volume":"81","author":"Str\u00e4hle","year":"2007","journal-title":"J. Virol."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1038\/s41401-020-0483-6","article-title":"Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients","volume":"41","author":"Su","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"e1005122","DOI":"10.1371\/journal.ppat.1005122","article-title":"Immunostimulatory defective viral genomes from respiratory syncytial virus promote a strong innate antiviral response during infection in mice and humans","volume":"11","author":"Sun","year":"2015","journal-title":"PLoS Pathog."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"e1003703","DOI":"10.1371\/journal.ppat.1003703","article-title":"Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity","volume":"9","author":"Tapia","year":"2013","journal-title":"PLoS Pathog."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.chom.2010.05.009","article-title":"Influenza virus evolution, host adaptation, and pandemic formation","volume":"7","author":"Taubenberger","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jcv.2018.02.005","article-title":"Antiviral resistance due to deletion in the neuraminidase gene and defective interfering-like viral polymerase basic 2 RNA of influenza a virus subtype H3N2","volume":"102","author":"Trebbien","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1128\/iai.37.2.439-444.1982","article-title":"Defective interfering particles of respiratory syncytial virus","volume":"37","author":"Treuhaft","year":"1982","journal-title":"Infect. Immun."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"e1006650","DOI":"10.1371\/journal.ppat.1006650","article-title":"Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients","volume":"13","author":"Vasilijevic","year":"2017","journal-title":"PLoS Pathog."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"186","DOI":"10.3390\/v9070186","article-title":"Targeting pattern recognition receptors (PRR) for vaccine Adjuvantation: from synthetic PRR agonists to the potential of defective interfering particles of viruses","volume":"9","author":"Vasou","year":"2017","journal-title":"Viruses"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/s41564-019-0465-y","article-title":"Defective viral genomes are key drivers of the virus-host interaction","volume":"4","author":"Vignuzzi","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"S47","DOI":"10.1002\/art.1780210906","article-title":"Persistent measles virus infection in vitro and in man","volume":"21","author":"Viola","year":"1978","journal-title":"Arthritis Rheum."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"11016","DOI":"10.1128\/JVI.05647-11","article-title":"In silico reconstruction of viral genomes from small RNAs improves virus-derived small interfering RNA profiling","volume":"85","author":"Vodovar","year":"2011","journal-title":"J. Virol."},{"key":"ref127","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S0065-3527(08)60529-1","article-title":"Incomplete forms of influenza virus","volume":"2","author":"Von Magnus","year":"1954","journal-title":"Adv. Virus Res."},{"key":"ref128","doi-asserted-by":"publisher","first-page":"115202","DOI":"10.1016\/j.jviromet.2025.115202","article-title":"Illumina MiSeq and iSeq platforms yield comparable results for viral genomic sequencing","volume":"338","author":"Wagner","year":"2025","journal-title":"J. Virol. Methods"},{"key":"ref129","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.chom.2024.01.014","article-title":"XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1","volume":"32","author":"Wang","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ref130","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s40246-024-00666-w","article-title":"Fast and accurate DNASeq variant calling workflow composed of LUSH toolkit","volume":"18","author":"Wang","year":"2024","journal-title":"Hum. Genomics"},{"key":"ref131","doi-asserted-by":"publisher","first-page":"10028","DOI":"10.1128\/JVI.77.18.10028-10036.2003","article-title":"Theoretical design of a gene therapy to prevent AIDS but not human immunodeficiency virus type 1 infection","volume":"77","author":"Weinberger","year":"2003","journal-title":"J. Virol."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"S460","DOI":"10.1093\/infdis\/jiz564","article-title":"Inhibition of Nipah virus by defective interfering particles","volume":"221","author":"Welch","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref133","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1021\/acs.molpharmaceut.0c00315","article-title":"Combined intranasal Nanoemulsion and RIG-I activating RNA adjuvants enhance mucosal, humoral, and cellular immunity to influenza virus","volume":"18","author":"Wong","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref134","doi-asserted-by":"publisher","first-page":"773","DOI":"10.3390\/v14122773","article-title":"Defective interfering particles of influenza virus and their characteristics, impacts, and use in vaccines and antiviral strategies: a systematic review","volume":"14","author":"Wu","year":"2022","journal-title":"Viruses"},{"key":"ref135","doi-asserted-by":"publisher","first-page":"6037","DOI":"10.1016\/j.cell.2021.11.023","article-title":"A defective viral genome strategy elicits broad protective immunity against respiratory viruses","volume":"184","author":"Xiao","year":"2021","journal-title":"Cell"},{"key":"ref136","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/s41467-017-00909-6","article-title":"Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence","volume":"8","author":"Xu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref137","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.3389\/fmicb.2019.01852","article-title":"The antiviral and antitumor effects of defective interfering particles\/genomes and their mechanisms","volume":"10","author":"Yang","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref138","doi-asserted-by":"publisher","first-page":"659419","DOI":"10.3389\/fimmu.2021.659419","article-title":"Quantification of cytokine storms during virus infections","volume":"12","author":"Yuan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref139","doi-asserted-by":"publisher","first-page":"1125246","DOI":"10.3389\/fimmu.2023.1125246","article-title":"The development of COVID-19 treatment","volume":"14","author":"Yuan","year":"2023","journal-title":"Front. Immunol."},{"key":"ref140","doi-asserted-by":"publisher","first-page":"18036","DOI":"10.1038\/nrdp.2018.36","article-title":"Hepatitis B virus infection","volume":"4","author":"Yuen","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref141","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v15091786","article-title":"COVID-19 vaccines over three years after the outbreak of the COVID-19 epidemic","volume":"15","author":"Zasada","year":"2023","journal-title":"Viruses"},{"key":"ref142","doi-asserted-by":"publisher","first-page":"e0025023","DOI":"10.1128\/mbio.00250-23","article-title":"Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection","volume":"14","author":"Zhou","year":"2023","journal-title":"MBio"},{"key":"ref143","doi-asserted-by":"publisher","first-page":"e0143124","DOI":"10.1128\/spectrum.01431-24","article-title":"An integrated strain-level analytic pipeline utilizing longitudinal metagenomic data","volume":"12","author":"Zhou","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref144","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.tim.2020.02.006","article-title":"Defective interfering particles of negative-Strand RNA viruses","volume":"28","author":"Ziegler","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref145","doi-asserted-by":"publisher","first-page":"2373521","DOI":"10.1080\/21645515.2024.2373521","article-title":"Innovations in cell culture-based influenza vaccine manufacturing - from static cultures to high cell density cultivations","volume":"20","author":"Zinnecker","year":"2024","journal-title":"Hum. Vaccin. Immunother."}],"updated-by":[{"DOI":"10.3389\/fmicb.2025.1670478","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000}}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1642520\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T14:56:20Z","timestamp":1754924180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1642520\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":145,"alternative-id":["10.3389\/fmicb.2025.1642520"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1642520","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]},"article-number":"1642520"}}