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Published on: January 26, 2019
DC-SIGN as a receptor for phleboviruses
Pierre-Yves Lozach1, Andreas Kühbacher, Roger Meier
1Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, CH-8093 Zurich, Switzerland. lozach@bc.biol.ethz.ch
Arthropod-borne phleboviruses use the DC-SIGN receptor on dendritic cells (DCs) to enter cells. This interaction is crucial for virus infection and provides a new target for antiviral strategies.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Bunyaviruses are transmitted through arthropod bites, with dermal dendritic cells (DCs) being the initial host cells.
- DC-SIGN, a C-type lectin, is highly expressed on dermal DCs and plays a role in immune responses.
Purpose of the Study:
- To investigate the role of DC-SIGN in the entry of arthropod-borne phleboviruses into DCs.
- To elucidate the mechanism of DC-SIGN mediated virus-receptor interactions during infection.
Main Methods:
- Utilized live-cell imaging to visualize virus-receptor interactions.
- Employed an endocytosis-defective DC-SIGN mutant to assess its role in virus uptake.
- Tracked virus trafficking post-internalization.
Main Results:
- Identified DC-SIGN as a direct binding receptor for phleboviruses, including Rift Valley fever and Uukuniemi viruses.
- Demonstrated that DC-SIGN mediates both attachment and endocytosis of viruses into DCs.
- Observed virus-induced clustering of DC-SIGN on the cell surface.
- Showed that internalized viruses traffic to late endosomes, separating from DC-SIGN.
Conclusions:
- Establishes DC-SIGN as a critical entry receptor for arthropod-borne phleboviruses.
- Provides real-time insights into virus-receptor dynamics during cellular entry.
- Highlights DC-SIGN as a potential target for therapeutic interventions against phlebovirus infections.
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