{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T01:27:21Z","timestamp":1783560441517,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Rabies, caused by rabies virus (RABV), is a fatal neurological disease that still causes more than 59,000 human deaths each year. Type III interferon IFN-\u03bbs are cytokines with type I IFN-like antiviral activities. Although IFN-\u03bb can restrict the infection for some viruses, especially intestinal viruses, the inhibitory effect against RABV infection remains undefined. In this study, the function of type III IFN against RABV infection was investigated. Initially, we found that IFN-\u03bb2 and IFN-\u03bb3 could inhibit RABV replication in cells. To characterize the role of IFN-\u03bb in RABV infection in a mouse model, recombinant RABVs expressing murine IFN-\u03bb2 or IFN-\u03bb3, termed as rB2c-IFN\u03bb2 or rB2c-IFN\u03bb3, respectively, were constructed and rescued. It was found that expression of IFN-\u03bb could reduce the pathogenicity of RABV and limit viral spread in the brains by different infection routes. Furthermore, expression of IFN-\u03bb could induce the activation of the JAK-STAT pathway, resulting in the production of interferon-stimulated genes (ISGs). It was also found that rRABVs expressing IFN-\u03bb could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. Consistently, IFN-\u03bb was found to maintain the integrity of tight junction (TJ) protein ZO-1 of BBB to alleviate neuroinflammation in a transwell model. Our study underscores the role of IFN-\u03bb in inhibiting RABV infection, which potentiates IFN-\u03bb as a possible therapeutic agent for the treatment of RABV infection.<\/jats:p>","DOI":"10.3390\/v12040405","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T03:58:39Z","timestamp":1586231919000},"page":"405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Interferon-\u03bb Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-9099","authenticated-orcid":false,"given":"Yingying","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Basic Medicine, Dali University, Dali 671600, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0569-8105","authenticated-orcid":false,"given":"Ling","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaochen","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yachun","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, 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Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen F.","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Department of Pathology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/S0140-6736(13)62707-5","article-title":"Current status of rabies and prospects for 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