{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:24:16Z","timestamp":1790065456931,"version":"4.0.1"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Research in Infectious Diseases","award":["8201"],"award-info":[{"award-number":["8201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Infection with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1) weakens resistance of Aspergillus fumigatus common reference strain Af293 biofilms in intermicrobial competition with Pseudomonas aeruginosa. We compared the sensitivity of two infected and one virus-free Af293 strains to antifungal drugs. All three were comparably sensitive to drugs affecting fungal membranes (voriconazole, amphotericin) or cell wall glucan synthesis (micafungin, caspofungin). In contrast, forming biofilms of virus-free Af293 were much more resistant than AfuPmV-1-infected Af293 to nikkomycin Z (NikZ), a drug inhibiting chitin synthase. The IC50 for NikZ on biofilms was between 3.8 and 7.5 \u00b5g\/mL for virus-free Af293 and 0.94\u20131.88 \u00b5g\/mL for infected strains. The IC50 for the virus-free A. fumigatus strain 10AF was ~2 \u00b5g\/mL in most experiments. NikZ also modestly affected the planktonic growth of infected Af293 more than the virus-free strain (MIC 50%, 2 and 4 \u00b5g\/mL, respectively). Virus-free Af293 biofilm showed increased metabolism, and fungus growing as biofilm or planktonically showed increased growth compared to infected; these differences do not explain the resistance of the virus-free fungus to NikZ. In summary, AfuPmV-1 infection sensitized A. fumigatus to NikZ, but did not affect response to drugs commonly used against A. fumigatus infection. Virus infection had a greater effect on NikZ inhibition of biofilm than planktonic growth.<\/jats:p>","DOI":"10.3390\/v15010197","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T02:06:03Z","timestamp":1673402763000},"page":"197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Polymycovirus Infection Sensitizes Aspergillus fumigatus for Antifungal Effects of Nikkomycin Z"],"prefix":"10.3390","volume":"15","author":[{"given":"Gabriele","family":"Sass","sequence":"first","affiliation":[{"name":"California Institute for Medical Research, San Jose, CA 95128, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3277-6359","authenticated-orcid":false,"given":"Ioly","family":"Kotta-Loizou","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK"},{"name":"Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield AL10 9AB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marife","family":"Martinez","sequence":"additional","affiliation":[{"name":"California Institute for Medical Research, San Jose, CA 95128, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-0483","authenticated-orcid":false,"given":"David J.","family":"Larwood","sequence":"additional","affiliation":[{"name":"Valley Fever Solutions, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stevens","sequence":"additional","affiliation":[{"name":"California Institute for Medical Research, San Jose, CA 95128, USA"},{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.3389\/fmicb.2017.01699","article-title":"Mycoviruses in Aspergilli: A comprehensive review","volume":"8","author":"Coutts","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.mib.2021.05.007","article-title":"Mycoviruses and their role in fungal pathogenesis","volume":"63","year":"2021","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9100","DOI":"10.1073\/pnas.1419225112","article-title":"A novel mycovirus from Aspergillus fumigatus contains four unique dsRNAs as its genome and is infectious as dsRNA","volume":"112","author":"Kanhayuwa","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kotta-Loizou, I., Coutts, R.H.A., and ICTV Report Consortium (2022). ICTV Virus Taxonomy Profile: Polymycoviridae 2022. J. Gen. Virol., 103.","DOI":"10.1099\/jgv.0.001747"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kotta-Loizou, I., and Coutts, R.H.A. (2017). Studies on the virome of the entomopathogenic fungus Beauveria bassiana reveal novel dsRNA elements and mild hypervirulence. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006183"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00450-20","DOI":"10.1128\/mBio.00450-20","article-title":"Hadaka virus 1: A capsidless eleven-segmented positive-sense single-stranded RNA virus from a phytopathogenic fungus, Fusarium oxysporum","volume":"11","author":"Sato","year":"2020","journal-title":"MBio"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41467-017-00237-9","article-title":"A dsRNA virus with filamentous viral particles","volume":"8","author":"Jia","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.1038\/s41598-018-23807-3","article-title":"Characterization of two novel mycoviruses from Penicillium digitatum and the related fungicide resistance analysis","volume":"8","author":"Niu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1038\/nature04332","article-title":"Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus","volume":"438","author":"Nierman","year":"2005","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nazik, H., Kotta-Loizou, I., Sass, G., Coutts, R.H.A., and Stevens, D.A. (2021). Virus infection of Aspergillus fumigatus compromises the fungus in intermicrobial competition. Viruses, 13.","DOI":"10.3390\/v13040686"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Patil, R.H., Kotta-Loizou, I., Palyzov\u00e1, A., Pluh\u00e1\u010dek, T., Coutts, R.H.A., Stevens, D.A., and Havl\u00ed\u010dek, V. (2021). Freeing Aspergillus fumigatus of Polymycovirus infection renders it more resistant to competition with Pseudomonas aeruginosa due to altered iron-acquiring tactics. J. Fungi., 7.","DOI":"10.3390\/jof7070497"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nazik, H., Sass, G., D\u00e9ziel, E., and Stevens, D.A. (2020). Aspergillus is inhibited by Pseudomonas aeruginosa volatiles. J. Fungi., 6.","DOI":"10.3390\/jof6030118"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Stevens, D.A., Kotta-Loizou, I., Martinez, M., Coutts, R.H.A., and Sass, G. (2022, January 2\u20133). Virus infection impairs fungal response to stress: Effect of salt. Proceedings of the Program of the 10th Advances Against Aspergillosis and Mucormycosis Meeting, Virtual. Abstract No. 13.","DOI":"10.3390\/v15030718"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1093\/infdis\/162.5.1151","article-title":"Restriction endonuclease analysis of total cellular DNA of Aspergillus fumigatus isolates of geographically and epidemiologically diverse origin","volume":"162","author":"Denning","year":"1990","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1128\/AAC.35.7.1329","article-title":"Efficacy of cilofungin alone and in combination with amphotericin B in a murine model of disseminated aspergillosis","volume":"35","author":"Denning","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ferreira, J.A., Penner, J.C., Moss, R.B., Haagensen, J.A., Clemons, K.V., Spormann, A.M., Nazik, H., Cohen, K., Banaei, N., and Carolino, E. (2015). Inhibition of Aspergillus fumigatus and its biofilm by Pseudomonas aeruginosa is dependent on the source, phenotype and growth conditions of the bacterium. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134692"},{"key":"ref_17","first-page":"4827","article-title":"Evaluation of a soluble tetrazolium\/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines","volume":"48","author":"Scudiero","year":"1988","journal-title":"Cancer Res."},{"key":"ref_18","unstructured":"(2008). Document M38-A2, Clinical and Laboratory Standards Institute."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0732-8893(92)90053-V","article-title":"In vitro susceptibility and synergy studies of Aspergillus species to conventional and new agents","volume":"15","author":"Denning","year":"1992","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_20","first-page":"450","article-title":"Diversity of mycoviruses in Aspergilli","volume":"Volume 4","author":"Bamford","year":"2021","journal-title":"Encyclopedia of Virology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zoll, J., Verweij, P.E., and Melchers, W.J.G. (2018). Discovery and characterization of novel Aspergillus fumigatus mycoviruses. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200511"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Refos, J.M., Vonk, A.G., Eadie, K., Lo-Ten-Foe, J.R., Verbrugh, H.A., van Diepeningen, A.D., and van de Sande, W.W.J. (2013). Doublestranded RNA mycovirus infection of Aspergillus fumigatus is not dependent on the genetic make-up of the host. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077381"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s11046-012-9556-5","article-title":"Incidence of dsRNA mycoviruses in a collection of Aspergillus fumigatus isolates","volume":"174","author":"Bhatti","year":"2012","journal-title":"Mycopathologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s10096-010-0946-7","article-title":"Mycoviruses: Future therapeutic agents of invasive fungal infections in humans?","volume":"29","author":"Netea","year":"2010","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"607795","DOI":"10.3389\/fmicb.2020.607795","article-title":"Phenotypic and molecular biological analysis of polymycovirus AfuPmV-1M from Aspergillus fumigatus: Reduced fungal virulence in a mouse infection model","volume":"11","author":"Shishido","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S179","DOI":"10.1093\/mmy\/myy073","article-title":"Mycovirus therapy for invasive pulmonary aspergillosis?","volume":"57","author":"Vonk","year":"2019","journal-title":"Med. Mycol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.fgb.2015.01.003","article-title":"Aspergillus fumigatus mycovirus causes mild hypervirulent effect on pathogenicity when tested on Galleria mellonella","volume":"76","author":"Ozkan","year":"2015","journal-title":"Fungal. Genet. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.fgb.2011.07.008","article-title":"The effects of dsRNA mycoviruses on growth and murine virulence of Aspergillus fumigatus","volume":"48","author":"Bhatti","year":"2011","journal-title":"Fungal. Genet. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105108","DOI":"10.1016\/j.bioorg.2021.105108","article-title":"Design, synthesis and biological evaluation of novel diazaspirodecanone derivatives containing piperidine-4-carboxamide as chitin synthase inhibitors and antifungal agents","volume":"114","author":"Ji","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10482-014-0181-9","article-title":"Effect of low shear modeled microgravity on phenotypic and central chitin metabolism in the filamentous fungi Aspergillus niger and Penicillium chrysogenum","volume":"106","author":"Sathishkumar","year":"2014","journal-title":"Antonie. Van Leeuwenhoek"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1099\/mic.0.27249-0","article-title":"The cell wall stress response in Aspergillus niger involves increased expression of the glutamine: Fructose-6-phosphate amidotransferase-encoding gene (gfaA) and increased deposition of chitin in the cell wall","volume":"150","author":"Ram","year":"2004","journal-title":"Microbiology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1111\/cmi.12612","article-title":"Cell wall integrity signalling in human pathogenic fungi","volume":"18","author":"Dichtl","year":"2016","journal-title":"Cell Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e02347-19","DOI":"10.1128\/AEM.02347-19","article-title":"The cell wall integrity pathway contributes to the early stages of Aspergillus fumigatus asexual development","volume":"86","author":"Rocha","year":"2020","journal-title":"Appl. Environ. Microbiol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/1\/197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:05:38Z","timestamp":1760119538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/1\/197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,10]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["v15010197"],"URL":"https:\/\/doi.org\/10.3390\/v15010197","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,10]]}}}