{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:23:54Z","timestamp":1789428234363,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"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":["2023YFC2307800"],"award-info":[{"award-number":["2023YFC2307800"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFF1304900"],"award-info":[{"award-number":["2023YFF1304900"]}]},{"name":"National Key Research and Development Program of China","award":["32161160303"],"award-info":[{"award-number":["32161160303"]}]},{"name":"National Key Research and Development Program of China","award":["0010\/2021\/AFJ"],"award-info":[{"award-number":["0010\/2021\/AFJ"]}]},{"name":"National Key Research and Development Program of China","award":["JCYJ20230807090212024"],"award-info":[{"award-number":["JCYJ20230807090212024"]}]},{"name":"National Key Research and Development Program of China","award":["JCYJ20220530140800001"],"award-info":[{"award-number":["JCYJ20220530140800001"]}]},{"name":"National Science Fund of China\u2015Science and Technology Development Fund of Macau SAR","award":["2023YFC2307800"],"award-info":[{"award-number":["2023YFC2307800"]}]},{"name":"National Science Fund of China\u2015Science and Technology Development Fund of Macau SAR","award":["2023YFF1304900"],"award-info":[{"award-number":["2023YFF1304900"]}]},{"name":"National Science Fund of China\u2015Science and Technology Development Fund of Macau SAR","award":["32161160303"],"award-info":[{"award-number":["32161160303"]}]},{"name":"National Science Fund of China\u2015Science and Technology Development Fund of Macau SAR","award":["0010\/2021\/AFJ"],"award-info":[{"award-number":["0010\/2021\/AFJ"]}]},{"name":"National Science Fund of China\u2015Science and Technology Development Fund of Macau SAR","award":["JCYJ20230807090212024"],"award-info":[{"award-number":["JCYJ20230807090212024"]}]},{"name":"National Science Fund of China\u2015Science and Technology Development Fund of Macau SAR","award":["JCYJ20220530140800001"],"award-info":[{"award-number":["JCYJ20220530140800001"]}]},{"name":"Shenzhen Science and Technology Program of China","award":["2023YFC2307800"],"award-info":[{"award-number":["2023YFC2307800"]}]},{"name":"Shenzhen Science and Technology Program of China","award":["2023YFF1304900"],"award-info":[{"award-number":["2023YFF1304900"]}]},{"name":"Shenzhen Science and Technology Program of China","award":["32161160303"],"award-info":[{"award-number":["32161160303"]}]},{"name":"Shenzhen Science and Technology Program of China","award":["0010\/2021\/AFJ"],"award-info":[{"award-number":["0010\/2021\/AFJ"]}]},{"name":"Shenzhen Science and Technology Program of China","award":["JCYJ20230807090212024"],"award-info":[{"award-number":["JCYJ20230807090212024"]}]},{"name":"Shenzhen Science and Technology Program of China","award":["JCYJ20220530140800001"],"award-info":[{"award-number":["JCYJ20220530140800001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes pathogen transmission; however, host cells continuously develop strategies to combat pathogen infection and transmission. Moreover, it is still unknown how host cells develop their defense strategies against tick-borne viruses during tick sucking. Here, we found that the tick saliva peptide HIDfsin2 enhanced the antiviral innate immunity of mouse macrophages by activating the Toll-like receptor 4 (TLR4) signaling pathway, thereby restricting tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) replication. HIDfsin2 was identified to interact with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles, effectively enhancing the activation of the nuclear factor kappa-B (NF-\u03baB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4. Expectedly, TLR4 knockout completely eliminated the promotion effect of HIDfsin2 on NF-\u03baB and type I interferon activation. Moreover, HIDfsin2 enhanced SFTSV replication in TLR4-knockout mouse macrophages, which is consistent with our recent report that HIDfsin2 hijacked p38 mitogen-activated protein kinase (MAPK) to promote the replication of tick-borne SFTSV in A549 and Huh7 cells (human cell lines) with low expression of TLR4. Together, these results provide new insights into the innate immune mechanism of host cells following tick bites. Our study also shows a rare molecular event relating to the mutual antagonism between tick-borne SFTSV and host cells mediated by the tick saliva peptide HIDfsin2 at the tick\u2013host\u2013virus interface.<\/jats:p>","DOI":"10.3390\/antibiotics13050449","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T06:14:42Z","timestamp":1715753682000},"page":"449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Tick Saliva Peptide HIDfsin2 TLR4-Dependently Inhibits the Tick-Borne Severe Fever with Thrombocytopenia Syndrome Virus in Mouse Macrophages"],"prefix":"10.3390","volume":"13","author":[{"given":"Luyao","family":"Wang","sequence":"first","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China"},{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"},{"name":"Shenzhen Research Institute, Wuhan University, Shenzhen 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishuo","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Pang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6988-1596","authenticated-orcid":false,"given":"Yiyuan","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingliang","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Cao","sequence":"additional","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China"},{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"},{"name":"Shenzhen Research Institute, Wuhan University, Shenzhen 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/s41467-021-21375-1","article-title":"Mapping ticks and tick-borne pathogens in China","volume":"12","author":"Zhao","year":"2021","journal-title":"Nat. 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