{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:06:40Z","timestamp":1779426400703,"version":"3.53.1"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Plant viruses need to use many host factors to establish infection. During the viral cycle, intracellular transport is fundamental to reach the plasmodesmata to enable cell-to-cell transport. Cucumovirus CMV (cucumber mosaic virus, CMV) can infect plants from most economically important crops. To identify additional host proteins involved in CMV movement in melon, we used the MP as a bait to screen a Yeast two-hybrid cDNA library from CMV-infected plants and identified a Niemann-Pick C1 (NPC1) protein as a novel MP interactor. NPC1 is a transmembrane protein involved in cholesterol transport in animal cells, but also in the infection by several viruses of different families. The identified clone from the melon NPC1 gene spans from exons 25 to 28 and includes two introns. Notably, deletion of the two introns and exon 28 does not impair the interaction capacity of the remaining peptide. The identified CmNPC1 gene maps to chromosome 11. In addition, the melon genome encodes a second copy of NPC1 in chromosome 7 (CmNPC1-C7), highly similar. Functional assays revealed that the interaction domain of CmNPC1-C7 also interacts with CMV MP, suggesting that both genes could have a role in CMV infection. This study represents the first report linking NPC1 to the infection process of a plant virus, expanding our understanding of plant\u2013virus interactions.<\/jats:p>","DOI":"10.3390\/v18050577","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:45:34Z","timestamp":1779291934000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Melon Sterol Transporter Niemann-Pick C1 Protein Is a New Interactor of Cucumber mosaic virus Movement Protein"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1336-7525","authenticated-orcid":false,"given":"N\u00faria","family":"Real","sequence":"first","affiliation":[{"name":"Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, C\/Vall Moronta, Edifici CRAG, Bellaterra (Cerdanyola del Vall\u00e9s), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-5655","authenticated-orcid":false,"given":"Irene","family":"Villar","sequence":"additional","affiliation":[{"name":"Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, C\/Vall Moronta, Edifici CRAG, Bellaterra (Cerdanyola del Vall\u00e9s), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0855-0213","authenticated-orcid":false,"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, C\/Vall Moronta, Edifici CRAG, Bellaterra (Cerdanyola del Vall\u00e9s), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manale","family":"Gajjout","sequence":"additional","affiliation":[{"name":"Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, C\/Vall Moronta, Edifici CRAG, Bellaterra (Cerdanyola del Vall\u00e9s), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-1469","authenticated-orcid":false,"given":"Weina","family":"Hou","sequence":"additional","affiliation":[{"name":"Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, C\/Vall Moronta, Edifici CRAG, Bellaterra (Cerdanyola del Vall\u00e9s), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-3847","authenticated-orcid":false,"given":"Ana Montserrat","family":"Mart\u00edn-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, C\/Vall Moronta, Edifici CRAG, Bellaterra (Cerdanyola del Vall\u00e9s), 08193 Barcelona, Spain"},{"name":"Institut de Recerca i Tecnologia Agroaliment\u00e0ries (IRTA), Campus UAB, Bellaterra, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.virol.2015.01.025","article-title":"Plant virus replication and movement","volume":"479\u2013480","author":"Heinlein","year":"2015","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hipper, C., Brault, V., Ziegler-Graff, V., and Revers, F. (2013). Viral and cellular factors involved in phloem transport of plant viruses. Front. Plant Sci., 4.","DOI":"10.3389\/fpls.2013.00154"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.aivir.2020.04.002","article-title":"Hijacking of host cellular components as proviral factors by plant-infecting viruses","volume":"107","author":"Hyodo","year":"2020","journal-title":"Adv. Virus Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Real, N., Garcia-Molina, A., Stolze, S.C., Harzen, A., Nakagami, H., and Mart\u00edn-Hern\u00e1ndez, A.M. (2025). Comprehensive proteomic profiling of Cucumber mosaic virus infection: Identifying key proteins and pathways involved in resistance and susceptibility in melon. BMC Plant Biol., 25.","DOI":"10.1186\/s12870-025-06464-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1055\/s-0040-1714414","article-title":"Advances in Transcriptomics in the Response to Stress in Plants","volume":"7","author":"Wang","year":"2020","journal-title":"Glob. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1021\/acs.jproteome.3c00069","article-title":"Profiling Plant Proteome and Transcriptome Changes during Grapevine Fanleaf Virus Infection","volume":"22","author":"Roy","year":"2023","journal-title":"J. Proteome Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1146\/annurev-phyto-121823-032017","article-title":"Replication Organelles of Plant Positive-Strand RNA Viruses: A Boost in Knowledge Following New Imaging Approaches","volume":"63","author":"Zhang","year":"2025","journal-title":"Annu. Rev. Phytopathol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"He, R., Li, Y., Bernards, M.A., and Wang, A. (2023). Manipulation of the Cellular Membrane-Cytoskeleton Network for RNA Virus Replication and Movement in Plants. Viruses, 15.","DOI":"10.3390\/v15030744"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.coviro.2021.03.007","article-title":"Tombusviruses orchestrate the host endomembrane system to create elaborate membranous replication organelles","volume":"48","author":"Nagy","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10460","DOI":"10.1128\/JVI.00819-09","article-title":"Turnip mosaic virus RNA replication complex vesicles are mobile, align with microfilaments, and are each derived from a single viral genome","volume":"83","author":"Cotton","year":"2009","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shimizu, Y., and Uemura, T. (2022). The sorting of cargo proteins in the plant trans-Golgi network. Front. Plant Sci., 13.","DOI":"10.3389\/fpls.2022.957995"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1094\/MPMI-23-3-0263","article-title":"The Intra- and intercellular movement of Melon necrotic spot virus (MNSV) depends on an active secretory pathway","volume":"23","author":"Navarro","year":"2010","journal-title":"Mol. Plant Microbe Interact."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wu, G., Jia, Z., Ding, K., Zheng, H., Lu, Y., Lin, L., Peng, J., Rao, S., Wang, A., and Chen, J. (2022). Turnip mosaic virus co-opts the vacuolar sorting receptor VSR4 to promote viral genome replication in plants by targeting viral replication vesicles to the endosome. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010257"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1093\/plphys\/kiac547","article-title":"A viral movement protein co-opts endoplasmic reticulum luminal-binding protein and calreticulin to promote intracellular movement","volume":"191","author":"Huang","year":"2023","journal-title":"Plant Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10471","DOI":"10.1038\/s41598-017-10783-3","article-title":"A mutation in the melon Vacuolar Protein Sorting 41 prevents systemic infection of Cucumber mosaic virus","volume":"7","author":"Giner","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.1093\/jxb\/erac135","article-title":"A single substitution in Vacuolar protein sorting 4 is responsible for resistance to Watermelon mosaic virus in melon","volume":"73","author":"Agaoua","year":"2022","journal-title":"J. Exp. Bot."},{"key":"ref_17","unstructured":"Edwardson, J.R., and Christie, R.G. (1991). Cucumoviruses. CRC Handbook of Viruses Infecting Legumes, CRC Press."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0065-3527(03)62005-1","article-title":"Cucumoviruses","volume":"62","author":"Palukaitis","year":"2003","journal-title":"Adv. Virus Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/B978-0-12-394314-9.00013-0","article-title":"Cucumber Mosasic Virus","volume":"84","author":"Jacquemond","year":"2012","journal-title":"Adv. Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s11032-014-0038-y","article-title":"The complex resistance to Cucumber mosaic cucumovirus (CMV) in the melon accession PI 161375 is governed by one gene and at least two quantitative trait loci","volume":"34","author":"Monforte","year":"2014","journal-title":"Mol. Breed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00122-008-0897-x","article-title":"Dissection of the oligogenic resistance to Cucumber mosaic virus in the melon accession PI 161375","volume":"118","author":"Essafi","year":"2009","journal-title":"Theor. Appl. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1242\/jcs.107805","article-title":"CORVET and HOPS tethering complexes\u2013coordinators of endosome and lysosome fusion","volume":"126","author":"Balderhaar","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pascual, L., Yan, J., Pujol, M., Monforte, A.J., Pic\u00f3, B., and Mart\u00edn-Hern\u00e1ndez, A.M. (2019). CmVPS41 Is a General Gatekeeper for Resistance to Cucumber Mosaic Virus Phloem Entry in Melon. Front. Plant Sci., 10.","DOI":"10.3389\/fpls.2019.01219"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/mpp.12225","article-title":"Four sequence positions of the movement protein of Cucumber mosaic virus determine the virulence against cmv1-mediated resistance in melon","volume":"16","year":"2015","journal-title":"Mol. Plant Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1111\/mpp.12351","article-title":"cmv1 is a gate for Cucumber mosaic virus transport from bundle sheath cells to phloem in melon","volume":"17","author":"Heinlein","year":"2016","journal-title":"Mol. Plant Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1093\/plphys\/kiac583","article-title":"Mutations in CmVPS41 controlling resistance to cucumber mosaic virus display specific subcellular localization","volume":"191","author":"Real","year":"2023","journal-title":"Plant Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Villar-\u00c1lvarez, D., Leastro, M.O., Pallas, V., and S\u00e1nchez-Navarro, J.\u00c1. (2024). Identification of Host Factors Interacting with Movement Proteins of the 30K Family in Nicotiana tabacum. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212251"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.01002-20","article-title":"Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry","volume":"94","author":"Bo","year":"2020","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1104\/pp.110.171785","article-title":"The KEEP ON GOING protein of Arabidopsis recruits the ENHANCED DISEASE RESISTANCE1 protein to trans-Golgi network\/early endosome vesicles","volume":"155","author":"Gu","year":"2011","journal-title":"Plant Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1365-2958.2006.05350.x","article-title":"The type III effector repertoire of Pseudomonas syringae pv. syringae B728a and its role in survival and disease on host and non-host plants","volume":"62","author":"Vinatzer","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/1097-0061(20000630)16:9<857::AID-YEA561>3.0.CO;2-B","article-title":"Rapid and reliable protein extraction from yeast","volume":"16","author":"Kushnirov","year":"2000","journal-title":"Yeast"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/nph.17283","article-title":"Several geranylgeranyl diphosphate synthase isoforms supply metabolic substrates for carotenoid biosynthesis in tomato","volume":"231","author":"Barja","year":"2021","journal-title":"New Phytol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8088","DOI":"10.1038\/s41598-018-26416-2","article-title":"An improved assembly and annotation of the melon (Cucumis melo L.) reference genome","volume":"8","author":"Ruggieri","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e1065","DOI":"10.1002\/cpz1.1065","article-title":"Using EMBL-EBI Services via Web Interface and Programmatically via Web Services","volume":"4","author":"Madeira","year":"2024","journal-title":"Curr. Protoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1093\/nar\/gkg563","article-title":"ExPASy: The proteomics server for in-depth protein knowledge and analysis","volume":"31","author":"Gasteiger","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kumari, R., Kumar, S., Singh, L., and Hallan, V. (2016). Movement Protein of Cucumber Mosaic Virus Associates with Apoplastic Ascorbate Oxidase. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163320"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"gkaf1434","DOI":"10.1093\/nar\/gkaf1434","article-title":"Transcriptome-wide analysis of Arabidopsis DICER-LIKE1 RNA substrates","volume":"54","author":"Bologna","year":"2026","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1093\/nar\/gkae387","article-title":"Arabidopsis AGO1 N-terminal extension acts as an essential hub for PRMT5 interaction and post-translational modifications","volume":"52","author":"Lavatelli","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Dubey, V., Bozorg, B., W\u00fcstner, D., and Khandelia, H. (2020). Cholesterol binding to the sterol-sensing region of Niemann Pick C1 protein confines dynamics of its N-terminal domain. PLoS Comput. Biol., 16.","DOI":"10.1371\/journal.pcbi.1007554"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1093\/pcp\/pcx193","article-title":"Melonet-DB, a Grand RNA-Seq Gene Expression Atlas in Melon (Cucumis melo L.)","volume":"59","author":"Yano","year":"2018","journal-title":"Plant Cell Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1111\/jipb.13951","article-title":"Decoding alternative splicing: A key player in plant biotic stress resistance","volume":"67","author":"Zhu","year":"2025","journal-title":"J. Integr. Plant Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8212","DOI":"10.1073\/pnas.1607795113","article-title":"Structure of human Niemann-Pick C1 protein","volume":"113","author":"Li","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1111\/j.1600-0854.2004.00241.x","article-title":"Ncr1p, the yeast ortholog of mammalian Niemann Pick C1 protein, is dispensable for endocytic transport","volume":"5","author":"Zhang","year":"2004","journal-title":"Traffic"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nature10348","article-title":"Ebola virus entry requires the cholesterol transporter Niemann-Pick C1","volume":"477","author":"Carette","year":"2011","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nature10380","article-title":"Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection","volume":"477","author":"Misasi","year":"2011","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.01196-17","article-title":"Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis","volume":"92","author":"Stoeck","year":"2018","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41564-020-0740-y","article-title":"Exosome mimicry by a HAVCR1-NPC1 pathway of endosomal fusion mediates hepatitis A virus infection","volume":"5","author":"Costafreda","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ortega-Gonzalez, P., Taylor, G., Jangra, R.K., Tenorio, R., Fernandez de Castro, I., Mainou, B.A., Orchard, R.C., Wilen, C.B., Brigleb, P.H., and Sojati, J. (2022). Reovirus infection is regulated by NPC1 and endosomal cholesterol homeostasis. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010322"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7982","DOI":"10.1128\/JVI.00259-09","article-title":"Deficiency of niemann-pick type C-1 protein impairs release of human immunodeficiency virus type 1 and results in Gag accumulation in late endosomal\/lysosomal compartments","volume":"83","author":"Tang","year":"2009","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13578-024-01331-4","article-title":"The inactivation of the Niemann Pick C1 cholesterol transporter restricts SARS-CoV-2 entry into host cells by decreasing ACE2 abundance at the plasma membrane","volume":"14","author":"Tiberi","year":"2024","journal-title":"Cell Biosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00425-015-2322-4","article-title":"Misexpression of the Niemann-Pick disease type C1 (NPC1)-like protein in Arabidopsis causes sphingolipid accumulation and reproductive defects","volume":"242","author":"Feldman","year":"2015","journal-title":"Planta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100147","DOI":"10.1016\/j.tcsw.2025.100147","article-title":"Sterols in plant biology\u2013Advances in studying membrane dynamics","volume":"13","author":"Vogel","year":"2025","journal-title":"Cell Surf."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/5\/577\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:21:02Z","timestamp":1779423662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/5\/577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["v18050577"],"URL":"https:\/\/doi.org\/10.3390\/v18050577","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]}}}