{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:03:20Z","timestamp":1790010200844,"version":"4.0.1"},"reference-count":53,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Shenzhen Medical Research Special Fund","award":["A2403001"],"award-info":[{"award-number":["A2403001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871688"],"award-info":[{"award-number":["81871688"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302556"],"award-info":[{"award-number":["82302556"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Nanshan District Major Health Science and Technology Program","award":["NSZD2023037"],"award-info":[{"award-number":["NSZD2023037"]}]},{"name":"Jiangsu Province Capability Improvement Project through Science, Technology, and Education","award":["ZDXYS202207"],"award-info":[{"award-number":["ZDXYS202207"]}]},{"name":"Open Project of National Health Commission Key Laboratory of Parasitic Disease Control and Prevention","award":["wk023-005"],"award-info":[{"award-number":["wk023-005"]}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2023A151501223"],"award-info":[{"award-number":["2023A151501223"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Nanshan District Key Project of Health Science and Technology Program","award":["NS2023005"],"award-info":[{"award-number":["NS2023005"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Mosquito cell lines are essential tools for arbovirus research. Endogenous viral elements (EVEs) are prevalent in mosquito genomes, yet their functional effects on host immune responses remain unclear, potentially complicating experimental interpretations. In this study, we systematically characterized endogenous mosquito densovirus-like elements (EMLs) within the\n                      <jats:italic toggle=\"yes\">Aedes aegypti<\/jats:italic>\n                      Aag2 cell line and found that these endogenous EMLs are transcriptionally active but translationally defective. The silencing of EML transcripts significantly diminished the replication of Zika virus (ZIKV), Japanese encephalitis virus (JEV), and chikungunya virus (CHIKV), while transiently increasing dengue virus 2 (DENV-2), thereby indicating a virus-dependent regulatory mechanism. Mechanistically, RNA sequencing after EML interference, alongside plasmid-based mimic expression, demonstrated that EML transcripts downregulate defensin A, an antimicrobial peptide produced by mosquitoes. Functional assays using synthetic defensin A showed that this peptide differentially regulates arboviral infection. Binding assays and structural modeling further supported its interaction with viral envelope proteins, while stage-restricted infection assays revealed distinct stages of action: defensin A enhanced adsorption of ZIKV, JEV, and CHIKV, but did not promote DENV-2 adsorption or entry, and instead reduced DENV-2 RNA accumulation at the post-entry replication stage. Our findings highlight a previously unrecognized role of densovirus-derived EVEs in mosquito innate immunity, extending their functional scope from the well-established PIWI-interacting RNA-mediated antiviral defense to the regulation of antimicrobial peptide-associated immune pathways. These findings emphasize the necessity of accounting for EVE activity when analyzing data derived from mosquito cell lines, and suggest that related EVE-mediated immune regulation may contribute to arbovirus dynamics in mosquitoes.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Mosquito-borne viruses such as dengue, Zika, Japanese encephalitis, and chikungunya continue to threaten human health worldwide. Laboratory studies often use\n                        <jats:italic toggle=\"yes\">Aedes aegypti<\/jats:italic>\n                        cell lines to investigate how these viruses interact with their mosquito hosts. Here, we show that the genomes of these cells contain endogenous viral elements derived from mosquito densoviruses. Far from being inert fossils, these sequences are transcriptionally active and regulate mosquito immunity by suppressing the antimicrobial peptide defensin A. This immune modulation influences the replication of different arboviruses in opposite ways, enhancing some while restricting others. Our findings reveal that integrated viral elements can shape the outcome of arbovirus infection, with important implications for interpreting mosquito cell culture experiments and for evaluating endogenous viral element-mediated immune regulation in mosquito\u2013virus interactions.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00520-26","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:01:16Z","timestamp":1789131676000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["MDV-like endogenous viral elements act as immune rheostats in\n                    <i>Aedes<\/i>\n                    cells by modulating defensin A-mediated responses to 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