Humanized mouse models of hantavirus-induced immunopathogenesis

• Applicant: Professor Dr. Günther Schönrich
• Subject Area: Virology ; Immunology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 274896046

Hantavirus reservoirs are observed throughout the world including Germany. Hantavirus infections can result in severe hemorrhagic fever. Thus, they are increasingly recognized as a threat for public health in Germany and also in other parts of the world. Similar to Ebolavirus infections neither vaccines nor antiviral therapies are available. The precise knowledge of the underlying disease mechanisms is vital to change this situation. Hantaviruses establish chronic infection in rodents and other small mammals. Due to their extensive adaption to these natural hosts they do not induce symptoms. Through inhalation of aerosolized excreta derived from infected small mammals hantaviruses can be transmitted to humans. In these dead-end hosts they cause an acute infection that can be linked with severe disease. Kidney failure, pulmonary edema or full blown hemorrhagic fever are observed. In addition, loss of platelets represents a hallmark of hantavirus-associated disease. Hantaviruses replicate in their human target cells without causing any cytopathic effect. For this reason, it is assumed that the human immune defense directed against hantaviruses itself causes the observed symptoms. In this proposal the immunological mechanisms that contribute to hantavirus-associated disease in humans will be investigated. For this purpose we have previously established humanized mouse models of hantavirus infection which are based on mice that harbor components of the human immune system. In this experimental systems we can now analyze by which mechanisms human immune cells eliminate the viruses and at the same time cause clinical symptoms. The experiments described here will shed light on mechanisms involved in hantavirus-induced immunopathogenesis. Moreover, they will lay the foundation for further translational studies that aim at development of rational therapeutic strategies and efficient vaccines. Finally, the hazard emanating from recently discovered novel hantaviruses with unknown pathogenic potential can be tested in these experimental systems.

• DFG Programme: Research Grants