Dendritic cell interactions for early dengue virus detection and disease understanding

Abstract

Dengue fever is an incurable mosquito-borne tropical disease initiated by the Dengue virus. This virus is spread by mosquitos mostly in tropical and subtropical areas of the world. Symptoms can evolve from fever and muscle/joint pains to life-threatening Dengue hemorrhagic fever characterized by increased vascular permeability, hemorrhage and shock. According to the World Health Organization, the number of people reported suffering from Dengue fever and/or Dengue hemorrhagic fever globally in the year 2000 to 2007 was ~ 968564. In Brazil, for the year 2017 alone the number of Dengue cases was 252054. There are currently no efficient drugs to treat and neither any efficient tool to properly understand and diagnose Dengue Hemorrhage fever in a timely fashion. Only limited progress has been made on Dengue diagnosis (ELISA) through antibody detection.In this project we will investigate virus-cell interactions, at different NS1 concentrations, using induced pluripotent stem cell (iPSC) derived midbrain dopaminergic neurons (mDANs). The dendritic cells are the most realistic and human relevant target of Dengue virus. The pathogenic roles of Dengue virus NS1 will be tested both chemically and electrically. In particular, the systems comprises 2 electrodes: (1) one low impedance rounded shape Au electrode and (2) one Aptamer-based electrode. Recordings of electroactive mDAN cells will occur while simultaneously monitoring NS1 concentrations through the Aptamer-based biosensors. Thus, studying the effect of Dengue virus NS1 on mDANs will contribute to our understanding of Dengue immune-pathogenesis for the development of anti-dengue therapeutics and vaccines. (AU)