Ponente
Descripción
Dengue virus (DENV) complex belongs to the family Flaviviridae, genus Flavivirus; four potentially deadly viruses recognized as serotypes form it. DENV1-4 can cause dengue, a disease with clinical manifestations that range from a flu-like febrile syndrome to a potentially fatal hypovolemic shock with hemorrhagic manifestations. There is an urgent need of effective and safe vaccines and antivirals to treat dengue and its severe forms with molecules with potent neutralizing activity against the four viral serotypes. Using a Proteomic approach our group has identified the Low-density lipoprotein receptor related protein-1 (LRP1) as a putative receptor for DENV entry in human cells (Huerta et al., 2007, 2014, 2016; Ramos et al., 2019). Here, we demonstrate a direct interaction of LRP1 with the four serotypes of DENV (Huerta et al., 2020). The interaction is mediated by ligand binding domains (LBD) of LRP1, with a predominant role the region known as cluster IV of LBD. On the virus, the domain III of the envelope protein shows has a pivotal role on the interaction with this receptor. DENV2 infection is effectively blocked in human hepatocytes and monocytes by recombinant LRP1 minireceptors and ligands. Results also show a direct relation between the expression of LRP1 and the efficiency of the infection with DENV2 in human hepatocytes and give foundation for the development of potent inhibitory molecules to control DENV infection based on the interference of the interaction with LRP1 receptor.
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Huerta, V. et al. (2014) Journal of General Virology, 95, pp. 2668–2676.
Huerta, V. et al. (2016) Journal of Proteomics, 131, pp. 205–213.
Ramos, Y. et al. (2019) Journal of Proteomics, 193, pp. 71–84.
Huerta, V. et al. (2020) BioRxiv 2020.06.10.144089.
