Type I interferon induction by respiratory viruses in vivo

Abstract

Type I interferons (IFN) are induced by virus infection of virtually all cell types, but the amount and duration of IFN-α/β synthesis can vary with the individual pathogen. In patients Influenza A virus is known to be a robust inducer of type I IFN production while respiratory syncytial virus (RSV) generates a poor type I IFN response. To determine whether this phenomenon of differential IFN induction could be reproduced in an animal model, lung and serum samples from BALB/c mice infected with influenza or RSV were assessed for IFN-α/β at various time points. Type I IFN was detected in mouse lung homogenates at 24 hours after infection with either virus, while only influenza induced serum IFN-α/β. Both viruses actively replicated in lung epithelium, and for influenza-infected mice, type I IFN levels paralleled rising virus titers. In contrast, RSV infection resulted in an initial burst of IFN-α/β synthesis at 24 hours, but then disappeared as the virus titers rose. This may reflect the slower rate of RSV replication and the resultant decrease in initiation of new infections when compared with influenza. These studies demonstrate that type I IFN production in an RSV-infected animal is very limited despite the ability of RSV and influenza to trigger equivalent responses in the first 24 hours following infection. Combined with the relative inability of RSV to stimulate IFN-α/β production by dendritic cells in vitro, these factors may explain the very early disappearance of IFN-α/β from the RSV infected host. This research is supported by NIH grants R01 AI047226 and R01 DC00648.