The limited role of the human interferon system response to respiratory syncytial virus challenge: analysis and comparison to influenza virus challenge

The respiratory syncytial virus (RSV)-induced production of interferon (IFN) by human macrophages and mononuclear leukocytes (MNL) and the sensitivities of RSV to subtypes of IFN-α were examined and compared to IFN production induced by influenza virus. Influenza virus induced high titers of total IFN bioactivity, transcription of the IFN-α1 and IFN-β gene products and production of IFN-γ. In contrast, RSV induced minimal or no detectable total IFN activity, and the absence of IFN bioactivity could not be attributed to inhibitors of IFN activity. There was no detectable transcription of IFN-α or IFN-β gene products by the cells exposed to RSV. RSV-exposed MNL did produce small amounts of IFN-γ, consistent with prior sensitization of the cell donors to the virus, but titers were substantially lower than those induced by influenza virus. RSV showed minimal but equivalent susceptibility to several subtypes of IFN-α. The data raise the possibility that the IFN system has a limited direct role in early host defense against RSV infection, but results should not be extrapolated directly to in vivo events.