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MCP-1 Reduction by L-SIGN Expression in Dengue Virus-Infected Liver Endothelial Cells
Keh-Sen Liu1, Lin Wang2, Po-Ming Chen3,4
1Division of Infectious Diseases, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
Abstract:
(1) Background: The C-type lectin domain family 4 member M (CLEC4M, also known as L-SIGN) is a crucial pathogen-recognition receptor for the dengue virus (DENV). Our previous study has exhibited a polymorphism in its extracellular neck region, specifically within the long tandem repeats of exon 4, which correlates with DHF in DENV infection and causes liver damage. (2) Methods: Using monocyte-derived dendritic cells (MDDCs) and SK-HEP1 liver endothelial cell lines to compare viral replication relative to L-SIGN expression. (3) Results: Results indicated that SK-HEP1 cells were more susceptible to DENV infection than MDDCs, and L-SIGN transfection significantly increased viral replication in SK-HEP1 cell lines. The study also found that L-SIGN-enhanced DENV infection is mediated by the decrease in monocyte chemoattractant protein-1 (MCP-1) but not interferon gamma inducible protein-10 (IP-10). These findings reveal that L-SIGN-induced DENV infection leads to reduced MCP-1 levels, which, in turn, enhances DENV replication velocity. (4) Conclusions: This study offers insights into the molecular mechanisms of DENV replication and identifies potential therapeutic targets involving MCP-1 and L-SIGN pathways.
Insights
The C-type lectin domain family 4 member M (CLEC4M), or L-SIGN, enhances dengue virus (DENV) replication by reducing monocyte chemoattractant protein-1 (MCP-1) levels. This discovery highlights L-SIGN and MCP-1 as potential therapeutic targets for DENV infection.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- C-type lectin domain family 4 member M (CLEC4M), also known as L-SIGN, is a key receptor for dengue virus (DENV) recognition.
- A previously identified polymorphism in L-SIGN's extracellular neck region is linked to dengue hemorrhagic fever (DHF) and liver damage in DENV-infected individuals.
Purpose of the Study:
- To investigate the role of L-SIGN in DENV replication using cellular models.
- To elucidate the molecular mechanisms by which L-SIGN influences DENV infection and associated immune responses.
Main Methods:
- Comparison of DENV replication in monocyte-derived dendritic cells (MDDCs) and SK-HEP1 liver endothelial cells with varying L-SIGN expression levels.
- Assessment of viral replication following L-SIGN transfection in SK-HEP1 cells.
- Analysis of the impact of L-SIGN on the expression of chemokines, including monocyte chemoattractant protein-1 (MCP-1) and interferon gamma inducible protein-10 (IP-10).
Main Results:
- SK-HEP1 cells demonstrated higher susceptibility to DENV infection compared to MDDCs.
- L-SIGN expression, particularly after transfection, significantly enhanced DENV replication in SK-HEP1 cells.
- L-SIGN-mediated enhancement of DENV infection was associated with a decrease in MCP-1 levels, but not IP-10.
Conclusions:
- L-SIGN facilitates DENV replication by downregulating MCP-1, thereby increasing viral proliferation.
- The L-SIGN and MCP-1 pathways represent potential therapeutic targets for managing DENV infection.
- This study provides crucial insights into the molecular mechanisms underlying DENV replication and pathogenesis.
