About
We are interested in identifying host genetic factors affecting the susceptibility of mice to infection by SARS-CoV-2 using Collaborative Cross (CC) mice. Since mice were not naturally susceptible to the first (Wuhan) strains of SARS-CoV-2 due to poor binding of the virus spike to the mouse cellular receptor ACE2, we have developed a mouse-adapted strain of SARS-CoV-2 by serial passaging. The MACo3 viral strain carries two mutations in the receptor binding site of the spike and has acquired the capacity to replicate in the lungs of any mouse strain.
In March 2021, in collaboration with Etienne Simon-Lorière, we were the first to report that Alpha, Beta and Gamma variants of concern (VOCs) had acquired mutations permitting the infection of mice, raising the possibility of secondary wild rodents reservoirs.
We have used the genetic diversity of CC mice to study host genetic factors controlling the severity of the illness induced by SARS-CoV-2 and found large variations in lung viral load and body weight loss after intranasal inoculation of MACo3. The identification of causative variants is underway.
We also use mice transgenic for the human ACE2 receptor.