{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:05:01Z","timestamp":1790435101948,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32000341"],"award-info":[{"award-number":["32000341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Viruses"],"abstract":"<jats:p>Currently, insecticides that target nicotinic acetylcholine receptors (nAChR) are widely used. Studies on the sublethal effects of insecticides have found that they can affect the amount of virus in insects. The mechanism by which insecticides affect insect virus load remain unclear. Here, we show that nAChR targeting insecticide can affect viral replication through the immune deficiency (IMD) pathway. We demonstrate that a low dose of spinosad (6.8 ng\/mL), acting as an antagonist to Drosophila melanogaster nicotinic acetylcholine receptor \u03b16 (D\u03b16), significantly elevates Drosophila melanogaster sigmavirus (DMelSV) virus titers in adults of Drosophila melanogaster. Conversely, a high dose of spinosad (50 ng\/mL), acting as an agonist to D\u03b16, substantially decreases viral load. This bidirectional regulation of virus levels is absent in D\u03b16-knockout flies, signifying the specificity of spinosad\u2019s action through D\u03b16. Furthermore, the knockdown of D\u03b16 results in decreased expression of genes in the IMD pathway, including dredd, imd, relish, and downstream antimicrobial peptide genes AttA and AttB, indicating a reduced innate immune response. Subsequent investigations reveal no significant difference in viral titers between relish mutant flies and D\u03b16-relish double mutants, suggesting that the IMD pathway\u2019s role in antiviral defense is dependent on D\u03b16. Collectively, our findings shed light on the intricate interplay between nAChR signaling and the IMD pathway in mediating antiviral immunity, highlighting the potential for nAChR-targeting compounds to inadvertently influence viral dynamics in insect hosts. This knowledge may inform the development of integrated pest management strategies that consider the broader ecological impact of insecticide use.<\/jats:p>","DOI":"10.3390\/v16040562","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T11:01:41Z","timestamp":1712142101000},"page":"562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nicotinic Acetylcholine Receptor Alpha6 Contributes to Antiviral Immunity via IMD Pathway in Drosophila melanogaster"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8309-7796","authenticated-orcid":false,"given":"Zhiying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Entomology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoju","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Entomology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9701-5326","authenticated-orcid":false,"given":"Wangpeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Entomology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0320-1110","authenticated-orcid":false,"given":"Chuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Entomology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1584\/jpestics.D17-019","article-title":"The invertebrate pharmacology of insecticides acting at nicotinic acetylcholine receptors","volume":"42","author":"Crossthwaite","year":"2017","journal-title":"J. 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