{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:05:25Z","timestamp":1760144725847,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Show Chwan Memorial Hospital, Taiwan","award":["R11028","KMUH112-2M23"],"award-info":[{"award-number":["R11028","KMUH112-2M23"]}]},{"name":"Kaohsiung Medical University Hospital, Taiwan","award":["R11028","KMUH112-2M23"],"award-info":[{"award-number":["R11028","KMUH112-2M23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>C-type lectins play a crucial role as pathogen-recognition receptors for the dengue virus, which is responsible for causing both dengue fever (DF) and dengue hemorrhagic fever (DHF). DHF is a serious illness caused by the dengue virus, which exists in four different serotypes: DEN-1, DEN-2, DEN-3, and DEN-4. We conducted a genetic association study, during a significant DEN-2 outbreak in southern Taiwan, to explore how variations in the neck-region length of L-SIGN (also known as CD209L, CD299, or CLEC4M) impact the severity of dengue infection. PCR genotyping was utilized to identify polymorphisms in variable-number tandem repeats. We constructed L-SIGN variants containing either 7- or 9-tandem repeats and transfected these constructs into K562 and U937 cells, and cytokine and chemokine levels were evaluated using enzyme-linked immunosorbent assays (ELISAs) following DEN-2 virus infection. The L-SIGN allele 9 was observed to correlate with a heightened risk of developing DHF. Subsequent results revealed that the 9-tandem repeat was linked to elevated viral load alongside predominant T-helper 2 (Th2) cell responses (IL-4 and IL-10) in K562 and U937 cells. Transfecting K562 cells in vitro with L-SIGN variants containing 7- and 9-tandem repeats confirmed that the 9-tandem repeat transfectants facilitated a higher dengue viral load accompanied by increased cytokine production (MCP-1, IL-6, and IL-8). Considering the higher prevalence of DHF and an increased frequency of the L-SIGN neck\u2019s 9-tandem repeat in the Taiwanese population, individuals with the 9-tandem repeat may necessitate more stringent protection against mosquito bites during dengue outbreaks in Taiwan.<\/jats:p>","DOI":"10.3390\/ijms25105497","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T12:02:23Z","timestamp":1715947343000},"page":"5497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Relationship between the Number of Repeats in the Neck Regions of L-SIGN and Augmented Virus Replication and Immune Responses in Dengue Hemorrhagic Fever"],"prefix":"10.3390","volume":"25","author":[{"given":"Keh-Sen","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-9615","authenticated-orcid":false,"given":"Po-Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan"},{"name":"Department of Nursing, College of Health Sciences, Central Taiwan University of Science and Technology, Taichung 406, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pojen Hospital, Kaohsiung 813, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ing-Kit","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuender D.","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of Medical Research, MacKay Memorial Hospital, Taipei 104, Taiwan"},{"name":"Departments of Pediatrics, MacKay Memorial Hospital, Taipei 104, Taiwan"},{"name":"Department of Medicine, MacKay Medical College, New Taipei 252, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7529-5390","authenticated-orcid":false,"given":"Rong-Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/j.jiph.2023.08.001","article-title":"Dengue overview: An updated systemic review","volume":"16","author":"Khan","year":"2023","journal-title":"J. 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