Protection of mice from lethal influenza: evidence that defective interfering virus modulates the immune response and not virus multiplication

Intranasal administration of defective interfering (DI) influenza virus (A/WSN) ensured the survival of 80 ~ of C3H mice otherwise lethally infected with WSN by the intranasal route, whereas a control group which received fl-propiolactone-inactivated DI virus in place of DI virus died at 7.4 days post-infection. DI virus-treated mice developed significantly less lung consolidation than controls although qualitatively the cellular pathology in the two groups was indistinguishable. Surprisingly, in view of the accepted mode of action of DI virus interference, multiplication of infectious virus in the lung, production of viral haemagglutinin (HA) antigen and neuraminidase, and the distribution and amount of viral antigen in cells as shown by immune labelling were unaffected by the presence of active DI virus. Furthermore, assays of lung extracts showed that DI virus was not stimulating significantly greater amounts of interferon than the control inactivated DI virus. An alternative explanation arises from the fact that the pathology of influenza in inbred mice is immune (T lymphocyte)-mediated. Thus, since there is no evidence that DI virus affects virus multiplication we suggest that DI virus is responsible for ameliorating the damaging host responses. Anothe