Several enveloped RNA viruses of the Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi-organ failure. VHF is precipitated by excessive pro-inflammatory cytokine response (‘cytokine storm’) that triggers the manifestations of severe symptoms. The molecular mechanisms underlying this uncontrolled cytokine response remain poorly understood.
Yellow Fever (YF) is the original VHF. YF virus (YFV) is a member of the Flavivirus genus, a group of viruses that also holds Dengue, West Nile and Zika viruses. Similar to Ebola hemorrhagic fever, cytokine dysregulation in YF is thought to mediate endothelial damage, disseminated intravascular coagulation and circulatory shock observed in the terminal stage of the disease.
Our objective is to define the mechanisms underlying excessive cytokine response in organs infected with pathogenic YFV and to determine how the vaccine strain controls this response, using virological, microscopic and biochemical assays combined with Next Generation Sequencing (NGS) methods.