Spatial-temporal control of acute murine coronavirus infection

Intranasal infection of mice with the mouse hepatitis virus (MHV) results in an acute infection of the upper and lower airways, brain and proximal lymphoid organs. While MHV establishes a mild pulmonary infection, the virus spreads rapidly via retrograde infection of olfactory neurons to the brain. Type I interferon responsiveness in macrophages has been shown to critically limit viral infection and prevent multi-organ, coronavirus-induced disease. The elimination of virus-infected cells in both the lungs and brain coincides with the activation of cytotoxic T cells, while B cells critically-prevent viral recrudescence. Notably, class-switched, neutralizing antibodies can be detected within days of infection, prior to the onset of germinal center responses. The relevant lymphoid organs and mechanisms supporting the early activation of B cells and directing their migration among infected organs is being assessed in this project.