Induction and role of type I and III interferons during SARS CoV2 infection

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

SARS-CoV-2 infection is a current threat to the world as the cause of the ongoing pandemic. SARS-CoV-2 infects the respiratory tract and spread to the lower airways where an inflammatory response results in the disease COVID-19. We have previously shown that detection of respiratory viruses by pattern recognition receptors drive interferon (IFN) responses that are beneficial for the host response by both inhibiting viral replication and driving an anti-viral inflammatory response. However, if the type I and III IFN response is dyregulated, an enhanced and detrimental lung inflammation can occur. It is very likely that the outcome of SARS-CoV-2 infection, and the magnitude of inflammation, is determined very early during the infection and this will be studied in this proposal. The responses in the lower airways early during infection is impossible to study in humans and therefore, the first part of this work will be to validate several mouse models. We will use humanised ACE2 mice and Adenovirus-delivery of hACE2 to epithelial cells. These models will be transferred to transgenic and knockout mouse models for determination of the induction, timing, source and role of type I and II IFNs in the inflammatory response during SARS-CoV-2 infection. In addition, a SARS-CoV-2 strain will be engineered by reverse genetics, deficient in IFN antagonising genes, that will be used to determine how the virus manipulates the IFN response. Such engineering could eventually contribute to a strategy for attenuated vaccines. In sum, this proposal will unveil a detailed understanding of how the detrimental inflammation during COVID-19 is initiated.

Publications

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Description This work on this award has just started but the main finding so far is that we can find signs of SARS-CoV-2 infection in one of the mouse models we are validating.
Exploitation Route As a big part of this award is to validate several mouse models for SARS-CoV-2 infection of mice, this will be used by many different researchers.
Sectors Healthcare