{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:03:07Z","timestamp":1777248187056,"version":"3.51.4"},"reference-count":67,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T00:00:00Z","timestamp":1611964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R56AI135770-01A1"],"award-info":[{"award-number":["1R56AI135770-01A1"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Defective interfering particles (DIPs) are naturally occurring products during virus replication in infected cells. DIPs contain defective viral genomes (DVGs) and interfere with replication and propagation of their corresponding standard viral genomes by competing for viral and cellular resources, as well as promoting innate immune antiviral responses. Consequently, for many different viruses, including mammarenaviruses, DIPs play key roles in the outcome of infection. Due to their ability to broadly interfere with viral replication, DIPs are attractive tools for the development of a new generation of biologics to target genetically diverse and rapidly evolving viruses. Here, we provide evidence that in cells infected with the Lassa fever (LF) vaccine candidate ML29, a reassortant that carries the nucleoprotein (NP) and glycoprotein (GP) dominant antigens of the pathogenic Lassa virus (LASV) together with the L polymerase and Z matrix protein of the non-pathogenic genetically related Mopeia virus (MOPV), L-derived truncated RNA species are readily detected following infection at low multiplicity of infection (MOI) or in persistently-infected cells originally infected at high MOI. In the present study, we show that expression of green fluorescent protein (GFP) driven by a tri-segmented form of the mammarenavirus lymphocytic choriomeningitis virus (r3LCMV-GFP\/GFP) was strongly inhibited in ML29-persistently infected cells, and that the magnitude of GFP suppression was dependent on the passage history of the ML29-persistently infected cells. In addition, we found that DIP-enriched ML29 was highly attenuated in immunocompetent CBA\/J mice and in Hartley guinea pigs. Likewise, STAT-1-\/- mice, a validated small animal model for human LF associated hearing loss sequelae, infected with DIP-enriched ML29 did not exhibit any hearing abnormalities throughout the observation period (62 days).<\/jats:p>","DOI":"10.3390\/v13020214","type":"journal-article","created":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T08:56:01Z","timestamp":1611996961000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Lassa Virus Vaccine Candidate ML29 Generates Truncated Viral RNAs Which Contribute to Interfering Activity and Attenuation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3630-0588","authenticated-orcid":false,"given":"Dylan M.","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Center for Predictive Medicine for Biodefense and Emerging Infectious diseases, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-410X","authenticated-orcid":false,"given":"Beatrice","family":"Cubitt","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tia L.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Center for Predictive Medicine for Biodefense and Emerging Infectious diseases, University of Louisville, Louisville, KY 40202, USA"},{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 402042, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-8115","authenticated-orcid":false,"given":"Juan Carlos","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6523-5116","authenticated-orcid":false,"given":"Igor S.","family":"Lukashevich","sequence":"additional","affiliation":[{"name":"Center for Predictive Medicine for Biodefense and Emerging Infectious diseases, University of Louisville, Louisville, KY 40202, USA"},{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 402042, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","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":"ref_2","doi-asserted-by":"crossref","unstructured":"Salazar-Bravo, J., Ruedas, L., and Yates, T. 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