Building a Better Mouse Model to Understand Infant Respiratory Syncytial Virus Disease

Abstract

Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infection in infants; and there are no vaccines or specific antiviral drugs against RSV. The pathogenesis of RSV remains elusive. This is partly due to the fact that the mouse is semi‐permissive for human RSV. The present study sought to determine if a better neonatal mouse model of RSV infection could be obtained using a recombinant virus in which the F protein of standard laboratory strain A2 was replaced with that from the line 19 isolate (rA2‐19F).Five‐day‐old pups were infected with A2 or rA2‐19F. rA2‐19F caused significantly more lung inflammation and mucus than A2. More type II T helper (Th2) cells and less type I (Th1) cells and effector CD8+ T cells (Tc1) were observed in the rA2‐19F infected lungs compared to A2. A cohort of infected neonates were allowed to mature to adulthood and reinfected with the same strain at 4 wks post primary infection. Similarly, secondary infection with rA2‐19F caused exaggerated Th2 and reduced Th1 and Tc1 responses. These immune responses during reinfection were associated with increased airway hyperreactivity, mucus hyperproduction and eosinophilia in rA2‐19F vs. A2 infected mice. The mechanisms are unknown, but are associated with higher pulmonary viral loads in rA2‐19F vs. A2 infected mice during primary infection.Therefore, rA2‐19F caused more severe lung pathologies and Th2 immune responses compared to A2, possibly due to higher lung titers during primary infection. The rA2‐19F strain represents a better neonatal mouse model of RSV infection.This work is supported by U.S. National Institutes of Health.