{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:04:57Z","timestamp":1790435097560,"version":"4.1.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Sand flies, which transmit diseases like leishmaniases, bartonellosis, and certain viruses, pose a significant public health threat. Our research focuses on the immune responses of <jats:italic>Lutzomyia longipalpis<\/jats:italic>, the primary vector for visceral leishmaniasis in the Americas. We use <jats:italic>L. longipalpis<\/jats:italic> LL5 cells as a model to study how sand flies respond to pathogens. These cells exhibit robust immune reactions, producing molecules mainly regulated by the Toll, IMD, Jak-STAT, and RNAi pathways. In previous studies, we detected a non-specific antiviral response in LL5 cells following double-stranded RNAs (dsRNAs) transfection. A previous complete secretome of these cells showed molecules resembling an interferon-like antiviral response when transfected with polyinosinic\u2013polycytidylic acid (poly I:C), a synthetic dsRNA analog. In the current study, we analyzed soluble proteins secreted by LL5 cells after poly I:C transfection. Using comparative mass spectrometry, we examined protein composition of conditioned media depleted of exosomes at 24\u00a0h and 48\u00a0h. Most proteins uniquely expressed in the transfected groups had low abundance compared to the overall expressed proteins. Interactome prediction analysis revealed that at 24\u00a0h, the proteins uniquely found in the secretome of the transfected group were involved in RNA degradation and purine metabolism, while at 48\u00a0h they were linked to ribosomal proteins and signaling pathways such as Hedgehog, Transforming Growth Factor-beta (TGF-\u03b2), and Wingless\/integrated (Wnt). We highlight increased abundance of the TGF-\u03b2-induced protein ig-h3 (24\u00a0h and 48\u00a0h), a Toll-like receptor 3 (48\u00a0h), and a hemocytin (48\u00a0h) in the secretion of transfected groups compared to the controls. We also performed an interaction analysis of proteins more secreted by the treated group at 24\u00a0h and 48\u00a0h. Unlike the interactome of uniquely identified proteins, few interactions were observed at 24\u00a0h, with a predominance of extracellular matrix and cell adhesion proteins. The set of proteins more secreted at 48\u00a0h presented more interactions than at 24\u00a0h, with emphasis on catabolic processes, including RNA degradation. These findings indicate that poly I:C transfection in LL5 cells induces the secretion of proteins involved in cellular defense and repair, revealing molecules involved in the LL5 non-specific antiviral response.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1638505","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T05:25:16Z","timestamp":1757568316000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomics analysis of soluble secreted proteins of Lutzomyia longipalpis LL5 cells transfected with a dsRNA viral mimic: insights into cellular defense and repair signals"],"prefix":"10.3389","volume":"15","author":[{"given":"Andrea","family":"Martins da Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya Violeta","family":"Llanos Salamanca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabricio Klerynton","family":"Marchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Jorge","family":"Tempone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Loza Telleria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara Maria","family":"Traub-Csek\u00f6","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"358","DOI":"10.4269\/ajtmh.1975.24.358","article-title":"Pacui virus, phlebotomine flies, and small mammals in Brazil: an epidemiological study","volume":"24","author":"Aitken","year":"1975","journal-title":"Am. J. Trop. Med. Hygiene"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011283","article-title":"Characterisation of the antiviral RNA interference response to Toscana virus in sand fly cells","volume":"19","author":"Alexander","year":"2023","journal-title":"PloS Pathog."},{"key":"B3","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/35099560","article-title":"Recognition of double-stranded RNA and activation of NF-\u03baB by Toll-like receptor 3","volume":"413","author":"Alexopoulou","year":"2001","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/J.ANTIVIRAL.2013.07.005","article-title":"Sandfly-borne phleboviruses of Eurasia and Africa: Epidemiology, genetic diversity, geographic range, control measures","volume":"100","author":"Alkan","year":"2013","journal-title":"Antiviral Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"11773","DOI":"10.1128\/JVI.01543-15","article-title":"Ecuador paraiso escondido virus, a new flavivirus isolated from new world sand flies in Ecuador, is the first representative of a novel clade in the genus flavivirus","volume":"89","author":"Alkan","year":"2015","journal-title":"J. Virol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"D898","DOI":"10.1093\/nar\/gkab929","article-title":"VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center","volume":"50","author":"Amos","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s00018-009-0161-9","article-title":"Insect chitinase and chitinase-like proteins","volume":"67","author":"Arakane","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg6165","article-title":"Targeting nucleotide metabolism as the nexus of viral infections, cancer, and the immune response","volume":"7","author":"Ariav","year":"2021","journal-title":"Sci. Adv."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4707","DOI":"10.3390\/v7082840","article-title":"Regulation of the host antiviral state by intercellular communications","volume":"7","author":"Assil","year":"2015","journal-title":"Viruses"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.662711","article-title":"The road less traveled? Unconventional protein secretion at parasite\u2013host interfaces","volume":"9","author":"Balmer","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000599","article-title":"A proteomic atlas of senescence-associated secretomes for aging biomarker development","volume":"18","author":"Basisty","year":"2020","journal-title":"PloS Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.molimm.2004.04.017","article-title":"The Notch and Sonic hedgehog signalling pathways in immunity","volume":"41","author":"Benson","year":"2004","journal-title":"Mol. Immunol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/v15061268","article-title":"Review on main arboviruses circulating on French Guiana, an ultra-peripheric european region in south america","volume":"15","author":"Bonifay","year":"2023","journal-title":"Viruses"},{"key":"B14","doi-asserted-by":"publisher","first-page":"6448","DOI":"10.1038\/s41598-017-06623-z","article-title":"Virus and dsRNA-triggered transcriptional responses reveal key components of honey bee antiviral defense","volume":"7","author":"Brutscher","year":"2017","journal-title":"Sci. Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/s0022-2836(65)80264-9","article-title":"Physical and chemical characterization of the ordered complexes formed between polyinosinic acid, polycytidylic acid and their deoxyribo-analogues","volume":"12","author":"Chamberlin","year":"1965","journal-title":"J. Mol. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1093\/jmedent\/29.2.368","article-title":"Titers of vesicular stomatitis virus, new Jersey serotype, in naturally infected male and female lutzomyia shannoni (Diptera: psychodidae) in Georgia","volume":"29","author":"Comer","year":"1992","journal-title":"J. Med. Entomology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"5202","DOI":"10.1093\/nar\/gku118","article-title":"Ribonuclease L and metal-ion\u2013independent endoribonuclease cleavage sites in host and viral RNAs","volume":"42","author":"Cooper","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"476","DOI":"10.4269\/ajtmh.1990.42.476","article-title":"Isolation of vesicular stomatitis virus new Jersey serotype from phlebotomine sand flies in Georgia","volume":"42","author":"Corn","year":"1990","journal-title":"Am. J. Trop. Med. Hygiene"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1021\/pr101065j","article-title":"Andromeda: a peptide search engine integrated into the MaxQuant environment","volume":"10","author":"Cox","year":"2011","journal-title":"J. Proteome Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/s41392-022-01175-9","article-title":"RNA modifications: importance in immune cell biology and related diseases","volume":"7","author":"Cui","year":"2022","journal-title":"Signal Transduction Targeted Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12964-022-00895-3","article-title":"Phospholipid scramblase 1: a protein with multiple functions via multiple molecular interactors","volume":"20","author":"Dal Col","year":"2022","journal-title":"Cell Communication Signaling"},{"key":"B23","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1186\/S13071-018-2985-3","article-title":"Viola phlebovirus is a novel Phlebotomus fever serogroup member identified in Lutzomyia (Lutzomyia) longipalpis from Brazilian Pantanal","volume":"11","author":"De Carvalho","year":"2018","journal-title":"Parasites Vectors"},{"key":"B24","doi-asserted-by":"publisher","first-page":"R406","DOI":"10.1016\/j.cub.2017.11.074","article-title":"Unconventional mechanisms of eukaryotic protein secretion","volume":"28","author":"Dimou","year":"2018","journal-title":"Curr. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ibmb.2019.04.005","article-title":"Molecular regulations of metabolism during immune response in insects","volume":"109","author":"Dolezal","year":"2019","journal-title":"Insect Biochem. Mol. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.redox.2015.07.008","article-title":"Antioxidant responses and cellular adjustments to oxidative stress","volume":"6","author":"Espinosa-Diez","year":"2015","journal-title":"Redox Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"D279","DOI":"10.1093\/nar\/gkv1344","article-title":"The Pfam protein families database: towards a more sustainable future","volume":"44","author":"Finn","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077263","article-title":"Non-specific dsRNA-mediated antiviral response in the honey bee","volume":"8","author":"Flenniken","year":"2013","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.semcdb.2012.01.019","article-title":"Protein degradation and the stress response","volume":"23","author":"Flick","year":"2012","journal-title":"Semin. Cell Dev. Biol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/v13010009","article-title":"Characterization of a novel mitovirus of the sand fly lutzomyia longipalpis using genomic and virus\u2013host interaction signatures","volume":"13","author":"Fonseca","year":"2021","journal-title":"Viruses"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2118871119","article-title":"Juvenile hormone-induced histone deacetylase 3 suppresses apoptosis to maintain larval midgut in the yellow fever mosquito","volume":"119","author":"Gaddelapati","year":"2022","journal-title":"Proc. Natl. Acad. Sci. United States America"},{"key":"B32","doi-asserted-by":"publisher","first-page":"385","DOI":"10.4269\/ajtmh.1966.15.385","article-title":"An ecological survey for arboviruses in almirante, Panama 1959\u20131962","volume":"15","author":"Galindo","year":"1966","journal-title":"Am. J. Trop. Med. Hygiene"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/s12861-018-0167-3","article-title":"Comparative analysis of FKBP family protein: Evaluation, structure, and function in mammals and Drosophila melanogaster","volume":"18","author":"Ghartey-Kwansah","year":"2018","journal-title":"BMC Dev. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12964-021-00730-1","article-title":"The exosome journey: from biogenesis to uptake and intracellular signalling","volume":"19","author":"Gurung","year":"2021","journal-title":"Cell Communication Signaling"},{"key":"B35","doi-asserted-by":"publisher","first-page":"W375","DOI":"10.1093\/nar\/gkh378","article-title":"PrediSi: prediction of signal peptides and their cleavage positions","volume":"32","author":"Hiller","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.cell.2009.01.019","article-title":"The many pathways of RNA degradation","volume":"136","author":"Houseley","year":"2009","journal-title":"Cell"},{"key":"B37","doi-asserted-by":"publisher","first-page":"359","DOI":"10.4269\/ajtmh.19-0717","article-title":"Genetic characterization of frijoles and chilibre species complex viruses (Genus phlebovirus; family phenuiviridae) and three unclassified new world phleboviruses","volume":"102","author":"Hughes","year":"2019","journal-title":"Am. J. Trop. Med. Hygiene"},{"key":"B38","doi-asserted-by":"publisher","first-page":"5634","DOI":"10.1073\/pnas.1600612113","article-title":"TGF-beta signaling in insects regulates metamorphosis via juvenile hormone biosynthesis","volume":"113","author":"Ishimaru","year":"2016","journal-title":"Proc. Natl. Acad. Sci. United States America"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001837","article-title":"The role of sand flies as vectors of viruses other than phleboviruses","volume":"104","author":"Jancarova","year":"2023","journal-title":"J. Gen. Virol."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"B41","doi-asserted-by":"publisher","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/v13081658","article-title":"Cross talk between viruses and insect cells cytoskeleton","volume":"13","author":"Khorramnejad","year":"2021","journal-title":"Viruses"},{"key":"B43","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1146\/annurev-ento-011613-162107","article-title":"Insect heat shock proteins during stress and diapause","volume":"60","author":"King","year":"2015","journal-title":"Annu. Rev. Entomology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"4921","DOI":"10.1016\/j.jmb.2013.10.006","article-title":"Insect antiviral innate immunity: pathways, effectors, and connections","volume":"425","author":"Kingsolver","year":"2013","journal-title":"J. Mol. Biol."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0012509","article-title":"Sand flies and Toscana virus: Intra-vector infection dynamics and impact on Phlebotomus perniciosus life-history traits","volume":"18","author":"Laroche","year":"2024","journal-title":"PloS Negl. Trop. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s13071-019-3433-8","article-title":"Mosquito antiviral defense mechanisms: a delicate balance between innate immunity and persistent viral infection","volume":"12","author":"Lee","year":"2019","journal-title":"Parasites Vectors"},{"key":"B47","doi-asserted-by":"publisher","first-page":"17312","DOI":"10.1074\/jbc.271.29.17312","article-title":"Proteolytic processing patterns of prosaposin in insect and mammalian cells","volume":"271","author":"Leonova","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B48","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/nrg2303","article-title":"Toll-like receptors \u2014 taking an evolutionary approach","volume":"9","author":"Leulier","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02521","article-title":"Functions of the WNT signaling network in shaping host responses to infection","volume":"10","author":"Ljungberg","year":"2019","journal-title":"Front. Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.immuni.2010.01.013","article-title":"Quantitative proteomics reveals subset-specific viral recognition in dendritic cells","volume":"32","author":"Luber","year":"2010","journal-title":"Immunity"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006851","article-title":"Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its nuclear import and thereby suppressing virus replication","volume":"14","author":"Luo","year":"2018","journal-title":"PloS Pathog."},{"key":"B52","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/j.1365-2915.2012.01034.x","article-title":"Phlebotomine sandflies and the spreading of leishmaniases and other diseases of public health concern","volume":"27","author":"Maroli","year":"2013","journal-title":"Med. Veterinary Entomology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.mib.2016.05.002","article-title":"The diversity of insect antiviral immunity: insights from viruses","volume":"32","author":"Marques","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114678","article-title":"An evolutionary perspective to innate antiviral immunity in animals","volume":"43","author":"Marques","year":"2024","journal-title":"Cell Rep."},{"key":"B55","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3390\/v10010043","article-title":"Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response","volume":"10","author":"Martins-da-Silva","year":"2018","journal-title":"Viruses"},{"key":"B56","doi-asserted-by":"publisher","first-page":"4007","DOI":"10.1016\/j.cell.2023.07.036","article-title":"TGF-\u03b2 signaling in health and disease","volume":"186","author":"Massagu\u00e9","year":"2023","journal-title":"Cell"},{"key":"B57","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.addr.2007.11.005","article-title":"TLR3: Interferon induction by double-stranded RNA including poly(I:C)","volume":"60","author":"Matsumoto","year":"2008","journal-title":"Advanced Drug Delivery Rev."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.4269\/ajtmh.2006.75.1151","article-title":"Venereal transmission of chandipura virus by phlebotomus papatasi (Scopoli)","volume":"75","author":"Mavale","year":"2006","journal-title":"Am. J. Trop. Med. Hygiene"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1111\/j.1600-0854.2006.00495.x","article-title":"Endoplasmic Reticulum and Golgi Complex: Contributions to, and Turnover by, Autophagy","volume":"7","author":"Mijaljica","year":"2006","journal-title":"Traffic"},{"key":"B60","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nri3877","article-title":"The cytoskeleton in cell-autonomous immunity: structural determinants of host defence","volume":"15","author":"Mostowy","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"18025","DOI":"10.3390\/pharmaceutics13111802","article-title":"Mesenchymal stromal cell secretome for the treatment of immune-mediated inflammatory diseases: latest trends in isolation, content optimization and delivery avenues","volume":"13","author":"Munoz-Perez","year":"2021","journal-title":"Pharmaceutics"},{"key":"B62","doi-asserted-by":"publisher","first-page":"R619","DOI":"10.1016\/j.cub.2021.01.036","article-title":"The cytoskeleton in phagocytosis and macropinocytosis","volume":"31","author":"Mylvaganam","year":"2021","journal-title":"Curr. Biol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1074\/mcp.T500030-MCP200","article-title":"Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap","volume":"4","author":"Olsen","year":"2005","journal-title":"Mol. Cell. Proteomics"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1099\/vir.0.029389-0","article-title":"Aguacate virus, a new antigenic complex of the genus Phlebovirus (family Bunyaviridae)","volume":"92","author":"Palacios","year":"2011","journal-title":"J. Gen. Virol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3811","DOI":"10.1128\/JVI.02275-10","article-title":"Characterization of the candiru antigenic complex (Bunyaviridae: phlebovirus), a highly diverse and reassorting group of viruses affecting humans in tropical america","volume":"85","author":"Palacios","year":"2011","journal-title":"J. Virol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1099\/vir.0.000170","article-title":"Characterization of the Punta Toro species complex (genus Phlebovirus, family Bunyaviridae)","volume":"96","author":"Palacios","year":"2015","journal-title":"J. Gen. Virol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/imm.12143","article-title":"Toll-like receptor 3 in viral pathogenesis: friend or foe","volume":"140","author":"Perales-Linares","year":"2013","journal-title":"Immunology"},{"key":"B68","doi-asserted-by":"publisher","first-page":"962S","DOI":"10.1093\/jn\/127.5.962S","article-title":"Oxidants and antioxidants in viral diseases: disease mechanisms and metabolic regulation","volume":"127","author":"Peterhans","year":"1997","journal-title":"J. Nutr."},{"key":"B69","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.dci.2007.06.008","article-title":"Non-specific antiviral response detected in RNA-treated cultured cells of the sandfly, Lutzomyia longipalpis","volume":"32","author":"Pitaluga","year":"2008","journal-title":"Dev. Comp. Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"W200","DOI":"10.1093\/nar\/gky448","article-title":"HMMER web server: 2018 update","volume":"46","author":"Potter","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1251204","article-title":"Elucidating the role of dsRNA sensing and Toll6 in antiviral responses of Culex quinquefasciatus cells","volume":"13","author":"Prince","year":"2023","journal-title":"Front. Cell. Infection Microbiol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/B978-0-12-811257-1.00003-6","article-title":"Chapter 3 - Replication and Expression Strategies of Viruses","author":"Rampersad","year":"2018","journal-title":"Viruses"},{"key":"B73","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/S0076-6879(05)01014-1","article-title":"Mosquito glutathione transferases","volume":"401","author":"Ranson","year":"2005","journal-title":"Methods Enzymology"},{"key":"B74","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1042\/bj0870039","article-title":"Phosphorus metabolism of the housefly (Musca domestica L.) during recovery from anoxia","volume":"87","author":"Ray","year":"1963","journal-title":"Biochem. J."},{"key":"B75","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1146\/annurev-ento-120811-153557","article-title":"Biology of phlebotomine sand flies as vectors of disease agents","volume":"58","author":"Ready","year":"2013","journal-title":"Annu. Rev. Entomology"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.629777","article-title":"Arthropods under pressure: stress responses and immunity at the pathogen-vector interface","volume":"11","author":"Rosche","year":"2021","journal-title":"Front. Immunol."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008524","article-title":"Imd pathway-specific immune assays reveal NF-\u03baB stimulation by viral RNA PAMPs in Aedes aEgypti Aag2 cells","volume":"15","author":"Russell","year":"2021","journal-title":"PloS Negl. Trop. Dis."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1_33","DOI":"10.11416\/jibs.78.1_33","article-title":"Sequence-nonspecific suppression of gene expression by double-stranded RNA in silkworm cultured cells","volume":"78","author":"Sakashita","year":"2009","journal-title":"J. Insect Biotechnol. Sericology"},{"key":"B79","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/82_2011_148","article-title":"ADARs, viruses and innate immunity","volume":"353","author":"Samuel","year":"2012","journal-title":"Curr. Topics Microbiol. Immunol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1042\/EBC20170087","article-title":"Fed-EXosome: extracellular vesicles and cell\u2013cell communication in metabolic regulation","volume":"62","author":"Samuelson","year":"2018","journal-title":"Essays Biochem."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3390\/v14050979","article-title":"Manipulation of host microtubule networks by viral microtubule-associated proteins","volume":"14","author":"Seo","year":"2022","journal-title":"Viruses"},{"key":"B82","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B83","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1093\/oxfordjournals.aje.a120720","article-title":"Vesicular stomatitis virus, Indiana type: An arbovirus infection of tropical sandflies and humans","volume":"86","author":"Shelokov","year":"1967","journal-title":"Am. J. Epidemiol."},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100856","article-title":"Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection","volume":"297","author":"Shen","year":"2021","journal-title":"J. Biol. Chem."},{"key":"B85","doi-asserted-by":"publisher","first-page":"9249","DOI":"10.1074\/jbc.M109.083725","article-title":"A Coronin7 homolog with functions in actin-driven processes","volume":"285","author":"Shina","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B86","doi-asserted-by":"publisher","first-page":"17059","DOI":"10.1038\/s41598-017-17134-2","article-title":"Comparative analysis of double-stranded RNA degradation and processing in insects","volume":"7","author":"Singh","year":"2017","journal-title":"Sci. Rep."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0293075","article-title":"Epigenetic weapons in plant-herbivore interactions: Sulforaphane disrupts histone deacetylases, gene expression, and larval development in Spodoptera exigua while the specialist feeder Trichoplusia ni is largely resistant to these effects","volume":"18","author":"Somers","year":"2023","journal-title":"PloS One"},{"key":"B88","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/s41392-024-01888-z","article-title":"Cell\u2013cell communication: new insights and clinical implications","volume":"9","author":"Su","year":"2024","journal-title":"Sig Transduct Target Ther."},{"key":"B89","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000943","article-title":"RNA virus replication complexes","volume":"6","author":"Tao","year":"2010","journal-title":"PloS Pathog."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3389\/fitd.2021.747820","article-title":"Leishmania infantum Infection Modulates the Jak-STAT Pathway in Lutzomyia longipalpis LL5 Embryonic Cells and Adult Females, and Affects Parasite Growth in the Sand Fly","volume":"2","author":"Telleria","year":"2021","journal-title":"Front. Trop. Dis."},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3390\/v16030395","article-title":"Rhabdoviral endogenous sequences identified in the leishmaniasis vector lutzomyia longipalpis are widespread in sandflies from south america","volume":"16","author":"Tempone","year":"2024","journal-title":"Viruses"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/j.addr.2010.09.012","article-title":"The Wnt signaling pathway in cellular proliferation and differentiation: A tale of two coactivators","volume":"62","author":"Teo","year":"2010","journal-title":"Advanced Drug Delivery Rev."},{"key":"B94","doi-asserted-by":"publisher","first-page":"653","DOI":"10.4269\/AJTMH.1987.36.653","article-title":"Natural infection of humans, animals, and phlebotomine sand flies with the alagoas serotype of vesicular stomatitis virus in Colombia","volume":"36","author":"Tesh","year":"1987","journal-title":"Am. J. Trop. Med. Hygiene"},{"key":"B95","doi-asserted-by":"publisher","first-page":"258","DOI":"10.4269\/ajtmh.1974.23.258","article-title":"Ecology of viruses isolated from Panamanian phlebotomine sandflies","volume":"23","author":"Tesh","year":"1974","journal-title":"Am. J. Trop. Med. Hygiene"},{"key":"B96","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/jmedent\/20.2.199","article-title":"Development of a continuous cell line from the sand fly Lutzomyia longipalpis (Diptera: Psychodidae), and its susceptibility to infection with arboviruses","volume":"20","author":"Tesh","year":"1983","journal-title":"J. Med. Entomol"},{"key":"B97","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1016\/j.biocel.2007.06.004","article-title":"TGFBIp\/\u03b2ig-h3 protein: A versatile matrix molecule induced by TGF-\u03b2","volume":"39","author":"Thapa","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s13071-016-1507-4","article-title":"The sandfly Lutzomyia longipalpis LL5 embryonic cell line has active Toll and Imd pathways and shows immune responses to bacteria, yeast and Leishmania","volume":"9","author":"Tinoco-Nunes","year":"2016","journal-title":"Parasites Vectors"},{"key":"B99","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1016\/j.biocel.2005.02.009","article-title":"Tripeptidyl-peptidase II: A multi-purpose peptidase","volume":"37","author":"Tomkinson","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"999","DOI":"10.4269\/ajtmh.1984.33.999","article-title":"Carajas and maraba viruses, two new vesiculoviruses isolated from phlebotomine sand flies in Brazil","volume":"33","author":"Travassos Da Rosa","year":"1984","journal-title":"Am. J. Trop. Med. Hygiene"},{"key":"B101","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1128\/JVI.00776-12","article-title":"Negevirus: a proposed new taxon of insect-specific viruses with wide geographic distribution","volume":"87","author":"Vasilakis","year":"2013","journal-title":"J. Virol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ydbio.2015.05.020","article-title":"Hedgehog signaling regulates imaginal cell differentiation in a basally branching holometabolous insect","volume":"404","author":"Villarreal","year":"2015","journal-title":"Dev. Biol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.tim.2018.06.008","article-title":"Exploitation of cytoskeletal networks during early viral infection","volume":"27","author":"Walsh","year":"2019","journal-title":"Trends Microbiol."},{"key":"B104","first-page":"287","article-title":"Chapter Six - Nucleic Acid Sensing in Invertebrate Antiviral Immunity","volume-title":"International Review of Cell and Molecular Biology","author":"Wang","year":"2019"},{"key":"B105","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.dci.2014.03.013","article-title":"Nucleic acid-induced antiviral immunity in invertebrates: An evolutionary perspective","volume":"48","author":"Wang","year":"2015","journal-title":"Dev. Comp. Immunol."},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1026887","article-title":"Ribosomal control in RNA virus-infected cells","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Microbiol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/tra.12137","article-title":"Viral subversion of nucleocytoplasmic trafficking","volume":"15","author":"Yarbrough","year":"2014","journal-title":"Traffic"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3390\/cells11193166","article-title":"Dynamics of actin cytoskeleton and their signaling pathways during cellular wound repair","volume":"11","author":"Yumura","year":"2022","journal-title":"Cells"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.947789","article-title":"Heat shock proteins and viral infection","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Immunol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.ibmb.2007.06.011","article-title":"Characterization of recombinant chitinase-like proteins of Drosophila melanogaster and Tribolium castaneum","volume":"38","author":"Zhu","year":"2008","journal-title":"Insect Biochem. Mol. Biol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1146\/annurev-ento-011019-025224","article-title":"Mechanisms, applications, and challenges of insect RNA interference","volume":"65","author":"Zhu","year":"2020","journal-title":"Annu. Rev. Entomology"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1038\/srep02069","article-title":"The Wnt signaling pathway is involved in the regulation of phagocytosis of virus in Drosophila","volume":"3","author":"Zhu","year":"2013","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1638505\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T05:25:19Z","timestamp":1757568319000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1638505\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":112,"alternative-id":["10.3389\/fcimb.2025.1638505"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1638505","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"article-number":"1638505"}}