In this recent release from JBC, Taipei researchers Liu et al. describe a potential model for pathogenesis for Dengue virus (DV) based on molecular mimicry of host endothelial cells. Despite the numerous theories proposed, little is currently known about the mechanism Dengue viral hemorrhaging.
After the observation that polyclonal anti-DV NS1 (nonstructural protein 1) antibodies react cross-react with endothelial cells under fluorescence microscopy, Liu et al generated over 100 monoclonal antibodies (mAbs) and screened for specific host-cell reactivity in human umbilical vein endothelial cells (HUVECs) and the NS1 of all Dengue serotypes. One mAb in particular, which they termed DB16-1, had the ability to strongly cross react with both HUVECs and NS1s by ELISA, immunofluorescence, and flow cytometry. This suggested that dengue viral protein NS1 , the target of DB16-1, served as a molecular mimic to some host cellular target protein, which potentially serves as a trigger for antibody-dependent autoimmunity. Liu et al. went on to test this hypothesis by identifying the cellular target of DB16-1--a protein they dubbed LYRIC (lysine-rich CEACAM1 co-isolated), AKA metadherin--by western blot, immunoprecipitation an mass spectrometry. The y further identified the specific epitope in both LYRIC and NS1s as the same consensus KXWB peptide motif found in both molecules.
So in this very very thorough (and presumably quite expensive and tedious) study, Liu et al. conclude that NS1 acts as a molecular mimic of LYRIC which can stimulate autoimmunity in the host and constribute to Dengue Hemorrhagic Fever and Dengue Hemorrhagic shock syndrome.
- Vy Tran
Liu I, Chiu C, Chen Y, Wu H. Molecular Mimicry of Human Endothelial Cell Antigen by Autoantibodies to Nonstructural Protein 1 of Dengue Virus. The Journal of Biological Chemistry VOL. 286, NO. 11, pp. 9726–9736, March 18, 2011