{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:54Z","timestamp":1792789554941,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871018"],"award-info":[{"award-number":["31871018"]}],"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":["32122008"],"award-info":[{"award-number":["32122008"]}],"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":["2021YFC2300200"],"award-info":[{"award-number":["2021YFC2300200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Plan of China","award":["31871018"],"award-info":[{"award-number":["31871018"]}]},{"name":"National Key Research and Development Plan of China","award":["32122008"],"award-info":[{"award-number":["32122008"]}]},{"name":"National Key Research and Development Plan of China","award":["2021YFC2300200"],"award-info":[{"award-number":["2021YFC2300200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Herpes simplex virus type I (HSV-1) infection is a potential risk factor involved in the Amyloid \u03b2 (A\u03b2) associated neuropathology. However, further understanding of the neuropathological effects of the HSV-1 infection is hampered by the limitations of existing infection models due to the distinct differences between human brains and other mammalians\u2019 brains. Here we generated cerebral organoid models derived from pluripotent stem cells to investigate the HSV-induced A\u03b2 associated neuropathology and the role of antiviral drugs in the phenotypic rescue. Our results identified that the HSV-1-infected cerebral organoids recapitulated A\u03b2 associated neuropathology including the multicellular A\u03b2 deposition, dysregulated endogenous AD mediators, reactive gliosis, neuroinflammation, and neural loss, indicating that cerebral organoids offer an opportunity for modeling the interaction of HSV-1 with the complex phenotypes across the genetic, cellular, and tissue levels of the human Alzheimer\u2019s disease (AD). Furthermore, we identified that two antiviral drugs, namely Ribavirin (RBV) and Valacyclovir (VCV), inhibited HSV-1 replication and rescued the neuropathological phenotypes associated with AD in the HSV-1-infected cerebral organoids, implying their therapeutic potential to slow down the progression of AD. Our study provides a high-fidelity human-relevant in-vitro HSV-1 infection model to reconstitute the multiscale neuropathological features associated with AD and discover therapeutic drug candidates relevant to the AD viral hypothesis.<\/jats:p>","DOI":"10.3390\/ijms23115981","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T08:50:22Z","timestamp":1653555022000},"page":"5981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Cerebral Organoids for Modeling of HSV-1-Induced-Amyloid \u03b2 Associated Neuropathology and Phenotypic Rescue"],"prefix":"10.3390","volume":"23","author":[{"given":"Haowen","family":"Qiao","sequence":"first","affiliation":[{"name":"Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moujian","family":"Guo","sequence":"additional","affiliation":[{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China"},{"name":"Institute of Medical Virology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhu","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Xu","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhentao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-6209","authenticated-orcid":false,"given":"Ying","family":"Wu","sequence":"additional","affiliation":[{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China"},{"name":"Institute of Medical Virology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6857-2211","authenticated-orcid":false,"given":"Pu","family":"Chen","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China"},{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2016). 2016 Alzheimer\u2019s disease facts and figures. 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