Defective interfering influenza virus inhibits immunopathological effects of infectious virus in the mouse.

Mice inoculated intranasally with a lethal dose of standard influenza virus die with an immune-mediated pneumonia but are protected by coinoculation with defective interfering (DI) virus. Here we show that recruitment of immune cells into the infected lung is halved by treatment with DI virus although the CD4+/CD8+ cell ratio is not affected. Responsiveness of lung T and B cells to lectins is inhibited by standard virus, but coinoculation of mice with DI virus causes a 13-fold increase in T-cell proliferation and up to a 100-fold increase in immunoglobulin production. This effect appears to be due to lymphocyte-specific DI virus-mediated interference, since there is no inhibition of virus multiplication in the lungs. The net result is a shift from a lethal to a beneficial immune response.