{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:18:13Z","timestamp":1790363893610,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Shandong Province, China","award":["ZR2022MH115"],"award-info":[{"award-number":["ZR2022MH115"]}]},{"name":"Natural Science Foundation of Shandong Province, China","award":["2023CXGC010711"],"award-info":[{"award-number":["2023CXGC010711"]}]},{"name":"Natural Science Foundation of Shandong Province, China","award":["ZR2023QC199"],"award-info":[{"award-number":["ZR2023QC199"]}]},{"name":"Shandong Province Key Research and Development Plan Major Scientific and Technological Innovation Project","award":["ZR2022MH115"],"award-info":[{"award-number":["ZR2022MH115"]}]},{"name":"Shandong Province Key Research and Development Plan Major Scientific and Technological Innovation Project","award":["2023CXGC010711"],"award-info":[{"award-number":["2023CXGC010711"]}]},{"name":"Shandong Province Key Research and Development Plan Major Scientific and Technological Innovation Project","award":["ZR2023QC199"],"award-info":[{"award-number":["ZR2023QC199"]}]},{"name":"Shandong Provincial Natural Science Foundation","award":["ZR2022MH115"],"award-info":[{"award-number":["ZR2022MH115"]}]},{"name":"Shandong Provincial Natural Science Foundation","award":["2023CXGC010711"],"award-info":[{"award-number":["2023CXGC010711"]}]},{"name":"Shandong Provincial Natural Science Foundation","award":["ZR2023QC199"],"award-info":[{"award-number":["ZR2023QC199"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Arboviruses, transmitted by blood-sucking arthropods, are responsible for significant human and animal diseases, including fever, hemorrhagic fever, and encephalitis, posing a serious threat to global public health. Nevertheless, research on the mechanisms of arbovirus infection and the development of therapeutic interventions has been impeded. This delay is primarily due to the limitations inherent in current in vitro research models, including cell cultures and animal models. The simplicity of cell types and interspecies differences present significant obstacles to advancing our understanding of arbovirus infection mechanisms and the development of effective drugs. Human brain organoids, derived from human pluripotent stem cells or human embryonic stem cells and cultured in three-dimensional systems, more accurately replicate the extensive neuronal cellular diversity and key characteristics of human neurodevelopment. These organoids serve as an ideal model for investigating the intricate interactions between viruses and human hosts, and providing a novel platform for the development of antiviral drugs. In this review, we summarize how brain organoid models complement classical approaches to accelerate research into the infection mechanisms of arboviruses, with a particular focus on the types of neural cells, key factors, and cellular signaling pathways involved in the arbovirus infection of brain organoids that have been reported. Furthermore, we examine the development of brain organoids, address their current limitations, and propose future directions to enhance the application of brain organoids in the study of arboviral infectious diseases.<\/jats:p>","DOI":"10.3390\/microorganisms13061281","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T03:19:38Z","timestamp":1748834378000},"page":"1281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Application and Challenges of Brain Organoids in Exploring the Mechanism of Arbovirus Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Baoqiu","family":"Cui","sequence":"first","affiliation":[{"name":"Center for Organoid and Genome Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Organoid and Genome Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anum","family":"Farid","sequence":"additional","affiliation":[{"name":"Center for Organoid and Genome Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Organoid and Genome Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyue","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Organoid and Genome Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naixia","family":"Ren","sequence":"additional","affiliation":[{"name":"Center for Organoid and Genome Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-2354","authenticated-orcid":false,"given":"Fengtang","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Organoid and Genome Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-4750","authenticated-orcid":false,"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Organoid and Genome Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70033","DOI":"10.1002\/rmv.70033","article-title":"Arbovirus Infections and Epigenetic Mechanisms; a Potential Therapeutic Target","volume":"35","author":"Wang","year":"2025","journal-title":"Rev. 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