{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:13:08Z","timestamp":1790356388054,"version":"4.1.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Zika virus (ZIKV) remains a significant public health threat due to its pronounced neurotropism linked to Congenital Zika Syndrome (CZS). Paradoxically, the same neurotropism also provides a unique opportunity for exploiting ZIKV as an oncolytic agent against malignant brain tumors such as glioma. However, achieving precise control of ZIKV replication in specific cell types or tissues remains a major challenge. Here, we show that the brain-specific and enriched microRNA, miR-124, is highly expressed in neural progenitor cells (NPCs) and neurons, but minimally expressed in glioma stem cells (GSCs) and differentiated glioma stem cells (DGCs). Based on these observations, we engineered a recombinant ZIKV containing a miR-124 target sequence (miR-124T) inserted into the 3\u2032 untranslated region (UTR) of the viral genome, generating the virus designated ZIKV-miR124T. ZIKV-miR124T exhibited a significantly attenuated phenotype across multiple mouse models, including adult A129 mice, BALB\/c neonates, and pregnant mice. Importantly, in an orthotopic glioma model, ZIKV-miR124T retained potent oncolytic activity while showing a markedly improved safety profile. Viral replication was strictly confined in the tumor region, with a ~1,000-fold reduction in viral load in non-tumoral brain regions compared to the well-established live-attenuated ZIKV (ZIKV-LAV). Furthermore, a single immunization with ZIKV-miR124T conferred effective protection against lethal ZIKV challenge and significantly reduced vertical transmission in pregnant mice. Collectively, our findings establish a strong proof of concept for a rational, miRNA-guided strategy to generate a next-generation ZIKV platform with dual potential as a safe live-attenuated vaccine and a precisely regulated oncolytic virus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>This study presents a crucial advancement in controlling the safety and function of neurotropic viruses. We engineered a dual-purpose ZIKV, ZIKV-miR124T, which is regulated by the brain-specific microRNA, miR-124. This design forces the virus to strongly self-suppress in healthy neural tissue, solving a major safety concern for ZIKV-based therapies. ZIKV-miR124T is shown to be a potent oncolytic agent against malignant glioma while also serving as a highly effective, safe live-attenuated vaccine against ZIKV infection, reducing vertical transmission to the fetus. Our work provides a strong demonstration of utilizing microRNA regulation to achieve precise viral tropism and attenuation, offering a valuable, generalizable strategy for the development of safer and more effective viral therapies and vaccines against neurotropic pathogens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00208-26","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:37:11Z","timestamp":1778855831000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["MicroRNA-124-targeted recombinant Zika virus: a dual-functional and safe candidate for vaccination and oncolytic virotherapy"],"prefix":"10.1128","volume":"100","author":[{"given":"Chao","family":"Zhou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bv3c993","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Pathogen and Biosecurity, Academy of 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