{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:38:38Z","timestamp":1776742718262,"version":"3.51.2"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFD1800102"],"award-info":[{"award-number":["2022YFD1800102"]}]},{"name":"National Key Research and Development Program of China","award":["32273040"],"award-info":[{"award-number":["32273040"]}]},{"name":"National Natural Science Foundation of China","award":["2022YFD1800102"],"award-info":[{"award-number":["2022YFD1800102"]}]},{"name":"National Natural Science Foundation of China","award":["32273040"],"award-info":[{"award-number":["32273040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Japanese encephalitis virus (JEV), a mosquito-borne zoonotic virus, is one of the most important causes of human viral encephalitis. JEV relies on various attachment or entry co-factors to enter host cells. Among these co-factors, hTIM-1 has been identified as an attachment factor to promote JEV infection through interacting with phosphatidylserine (PS) on the viral envelope. However, the reasons why JEV prefers to use hTIM-1 over other PS binding receptors are unknown. Here, we demonstrated that hTIM-1 can directly interact with JEV E protein. The interaction between hTIM-1 and JEV relies on specific binding sites, respectively, ND114115 in the hTIM-1 IgV domain and K38 of the E protein. Furthermore, during the early stage of infection, hTIM-1 and JEV are co-internalized into cells and transported into early and late endosomes. Additionally, we found that the hTIM-1 soluble ectodomain protein effectively inhibits JEV infection in vitro. Moreover, hTIM-1-specific antibodies have been shown to downregulate JEV infectivity in cells. Taken together, these findings suggested that hTIM-1 protein directly interacts with JEV E protein and mediates JEV infection, in addition to the PS-TIM-1 interaction.<\/jats:p>","DOI":"10.3390\/v15071589","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:57:30Z","timestamp":1690160250000},"page":"1589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Interaction between hTIM-1 and Envelope Protein Is Important for JEV Infection"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhenjie","family":"Liang","sequence":"first","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhui","family":"Pan","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengda","family":"Xie","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingmiao","family":"Yang","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-8030","authenticated-orcid":false,"given":"Ruibing","family":"Cao","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2471\/BLT.10.085233","article-title":"Estimated global incidence of Japanese encephalitis: A systematic review","volume":"89","author":"Campbell","year":"2011","journal-title":"Bull. 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Spectr."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/7\/1589\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:16:24Z","timestamp":1760127384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/7\/1589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["v15071589"],"URL":"https:\/\/doi.org\/10.3390\/v15071589","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,21]]}}}