UC San Diego

With an estimated 3.9 billion people at risk of dengue fever, dengue is a major disease threat. Other flaviviruses such as Yellow fever virus (YFV), Japanese encephalitis virus (JEV), Zika virus (ZIKV), West Nile virus (WNV) amongst others, also have a significant burden of disease. For this reason, a model was built that optimizes viral infection in dendritic cells (DCs). DCs are the link between the innate and adaptive immunity and flaviviruses such as DENV, ZIKV YFV, JEV are capable of infecting DCs. Therefore, identifying mechanisms that mediate infection is important to understanding disease progression. We cell sorted populations of infected and bystander cells and collected RNA of DCs of all these populations. RNA-sequencing (RNA-seq) results indicated that despite similarities in the genome of ZIKV and DENV, they upregulated different pathways. ZIKV upregulated lipid metabolism and DENV upregulated inflammatory pathways when compared against mock. Infection models were similarly created with YFV and JEV vaccine strains. Our infection model, when coupled to a cell sort method provides a powerful method for identifying pro- or anti-viral mechanism from pure infected and uninfected populations.