Track 19: Role of host innate immune responses and arbovirus innate immune evasion in transmissibility, host range and disease outcome
Erik Snijder (LUMC)
Marjolein Kikkert (LUMC); Martijn van Hemert (LUMC)
Leiden University Medical Centre
The innate immune system functions as the first line of defense against invading pathogens including arboviruses such as Usutu virus and West Nile virus. In order to facilitate their replication in the host cell, many viruses have developed mechanisms to counteract the innate immune response of the cell. In my project we aim to identify these arbovirus evasion mechanisms and to define the key innate immune pathways involved in transmissibility and disease outcome. This knowledge might aid in predicting virulence factors of new emerging arboviruses and may be used in the development of live-attenuated vaccines.
So far we have characterized the proteins of Usutu virus that are involved in counteracting the interferon response, an important antiviral defense system of the cell. Currently, we are trying to understand in more detail how these viral proteins block the interferon response and we will check how this might affect disease severity. In addition, to better study the interaction of arboviruses with the host innate immune system we are trying to set up 3D models that more closely resemble the architecture and function of tissues/organs in our body. The initial site of infection for arboviruses is the skin. Therefore, we are developing a human skin equivalent model to study this first encounter of the virus with the host innate immune system.
This project 'Preparing for vector-borne virus outbreaks in a changing world: a One Health Approach' (NWA. 1160.1S.210) is (partly) financed by the Dutch Research Council (NWO).