Relationship between the Number of Repeats in the Neck Regions of L-SIGN and Augmented Virus Replication and Immune Responses in Dengue Hemorrhagic Fever

被引：1

作者：

Liu, Keh-Sen ^{[1
]}

Chen, Po-Ming ^{[2
,3
]}

Wang, Lin ^{[4
]}

Lee, Ing-Kit ^{[5
]}

Yang, Kuender D. ^{[6
,7
,8
]}

Chen, Rong-Fu ^{[9
,10
]}

机构：

[1] Show Chwan Mem Hosp, Dept Internal Med, Div Infect Dis, Changhua 500, Taiwan

[2] Show Chwan Mem Hosp, Res Assistant Ctr, Changhua 500, Taiwan

[3] Cent Taiwan Univ Sci & Technol, Coll Hlth Sci, Dept Nursing, Taichung 406, Taiwan

[4] Pojen Hosp, Dept Pediat, Kaohsiung 813, Taiwan

[5] Chang Gung Univ, Dept Internal Med, Div Infect Dis, Chang Gung Mem Hosp,Kaohsiung Med Ctr,Coll Med, Kaohsiung 833, Taiwan

[6] MacKay Mem Hosp, Dept Med Res, Taipei 104, Taiwan

[7] MacKay Mem Hosp, Dept Pediat, Taipei 104, Taiwan

[8] MacKay Med Coll, Dept Med, Taipei 252, Taiwan

[9] Kaohsiung Med Univ Hosp, Dept Surg, Div Plast Surg, Kaohsiung 807, Taiwan

[10] Kaohsiung Med Univ, Regenerat Med & Cell Therapy Res Ctr, Kaohsiung 807, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 10期

关键词：

L-SIGN; tandem repeats; dengue hemorrhagic fever; T-helper; 2; cells; HEPATITIS-C VIRUS; DC-SIGN; ENDOTHELIAL-CELLS; DENDRITIC CELLS; ADHESION; NONINTEGRIN; INFECTION; MOLECULE; POLYMORPHISMS; ICAM-3;

D O I：

10.3390/ijms25105497

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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's 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.

引用

页数：13