{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:10:27Z","timestamp":1764785427461,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Veterinary Medicine Stanley L. Adler Research Fund, Washington State University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Insects"],"abstract":"<jats:p>The arbovirus West Nile virus (WNV) is a danger to global health. Spread primarily by mosquitoes, WNV causes about 2000 cases per year in the United States. The natural mosquito immune response controls viral replication so that the host survives but can still transmit the virus. Using the genetically malleable Drosophila melanogaster model, we previously dissected innate immune pathways used to control WNV infection. Specifically, we showed that insulin\/IGF-1 signaling (IIS) activates a JAK\/STAT-mediated immune response that reduces WNV. However, how factors that regulate IIS in insects control infection has not been identified. D. melanogaster Limostatin (Lst) encodes a peptide hormone that suppresses insulin secretion. Its mammalian ortholog, Neuromedin U (NMU), is a peptide that regulates the production and secretion of insulin from pancreatic beta cells. In this study, we used D. melanogaster and human cell culture models to investigate the roles of these insulin regulators in immune signaling. We found that D. melanogaster Lst mutants, which have elevated insulin-like peptide expression, are less susceptible to WNV infection. Increased levels of insulin-like peptides in these flies result in upregulated JAK\/STAT activity, leading to protection from infection. Treatment of human cells with the insulin regulator NMU results in increased WNV replication. Further investigation of methods to target Lst in mosquitoes or NMU in mammals can improve vector control methods and may lead to improved therapeutics for human and animal infection.<\/jats:p>","DOI":"10.3390\/insects15060446","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T06:23:11Z","timestamp":1718259791000},"page":"446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Drosophila melanogaster Limostatin and Its Human Ortholog Promote West Nile Virus Infection"],"prefix":"10.3390","volume":"15","author":[{"given":"Ezra B.","family":"Mead","sequence":"first","affiliation":[{"name":"School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chasity E.","family":"Trammell","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"},{"name":"Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-332X","authenticated-orcid":false,"given":"Alan G.","family":"Goodman","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"},{"name":"Paul G. Allen School of Global Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/tbed.12888","article-title":"First Isolation of West Nile Virus in Zambia from Mosquitoes","volume":"65","author":"Orba","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_2","first-page":"344","article-title":"The outbreak of West Nile virus infection in the New York City are in 1999","volume":"24","author":"Nash","year":"2001","journal-title":"N. Engl. J. 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