The gammaherpesvirus chemokine binding protein binds to the N terminus of CXCL8
Louise M C Webb1, Ian Clark-Lewis, Antonio Alcami
1Department of Medicine, Division of Virology, University of Cambridge, Cambridge, United Kingdom.
Journal of Virology
|July 15, 2003
Abstract:
Viruses encode proteins that disrupt chemokine responses. The murine gammaherpesvirus 68 gene M3 encodes a chemokine binding protein (vCKBP-3) which has no sequence similarity to chemokine receptors but inhibits chemokine receptor binding and activity. We have used a panel of CXCL8 analogs to identify the structural requirements for CXCL8 to bind to vCKBP-3 in a scintillation proximity assay. Our data suggest that vCKBP-3 acts by mimicking the binding of chemokine receptors to CXCL8.
Insights
Murine gammaherpesvirus 68
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Viruses encode proteins that interfere with host chemokine signaling pathways.
- Murine gammaherpesvirus 68 (MHV-68) utilizes gene M3 to express a viral chemokine binding protein (vCKBP-3).
- vCKBP-3 lacks sequence homology to host chemokine receptors but modulates chemokine activity.
Purpose of the Study:
- To elucidate the structural basis for the interaction between the chemokine CXCL8 and vCKBP-3.
- To identify specific structural requirements of CXCL8 for binding to vCKBP-3.
- To understand the mechanism by which vCKBP-3 inhibits chemokine function.
Main Methods:
- Utilized a panel of modified CXCL8 analogs.
- Employed scintillation proximity assays to measure binding affinity.
- Analyzed structural interactions between CXCL8 variants and vCKBP-3.
Main Results:
- Identified key structural features of CXCL8 essential for vCKBP-3 binding.
- Demonstrated that vCKBP-3 effectively inhibits CXCL8 binding to its cognate receptors.
- Data suggest vCKBP-3 functions by mimicking the interaction interface of chemokine receptors.
Conclusions:
- vCKBP-3 from murine gammaherpesvirus 68 targets CXCL8 through a mechanism of molecular mimicry.
- Understanding these viral protein-chemokine interactions provides insights into viral immune evasion strategies.
- This study highlights vCKBP-3 as a potential target for therapeutic intervention against viral infections.
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