Journal of Glycobiology
Open Access
ISSN: 2168-958X
+44 1478 350008
ISSN: 2168-958X
+44 1478 350008
Dayron Martin Prieto
Center for Genetic Engineering and Biotechnology, Cuba
Posters & Accepted Abstracts: J Glycobiol
Dengue disease can be caused by any of the four virus serotypes of dengue virus complex i.e., DV1-4. Symptomatic dengue disease can vary from very mild symptoms to a life threatening syndrome with hemorrhagic manifestations. The interplay between viral and host factors that determine virus pathogenesis is not well understood. In previous work, a proteomic approach was used to study DV interactome in human plasma. Results pointed to inter alpha trypsin inhibitor complexes (I�±Ic) as putative interaction partners of DV. I�±Ic consist of protein-glycosaminoglycan-protein structures, containing serum derived Hyaluronan Associated Proteins (SHAP), covalently linked by a chondroitin sulfate chain (CS) with a serine protease inhibitor named Bikunin. SHAP bind covalently to hyaluronic acid in extracellular matrix, enhancing leukocytes adhesion during acute inflammatory response, a process typically altered in patients with severe dengue. Plasma levels of I�±Ic are lower in children infected with DV and the magnitude of the decrease correlate with disease severity. In this work, I�±Ic were highly purified from human plasma and identified by mass spectrometry. I�±Ic components were separated by chemical hydrolysis of CS and used to further validate and characterize the direct interaction with recombinant proteins comprising the domain III of the envelope protein of DV1-4: DIIIE1-4. Two types of independent interactions were identified; one of low affinity with the light chain Bikunin, presumably via the CS chain of this protein and a stronger interaction was found with SHAP. Our results suggest the direct participation of I�±Ic in the pathogenesis of DV1-4 infection in humans.
Email: dayron.martin@cigb.edu.cu