Sendai virus (SeV) accessory protein C limits the generation of double-stranded RNAs, defective interfering RNAs, or both during viral transcription and replication, thereby limiting interferon-β production. Our recent in vitro analyses on murine macrophage cell lines demonstrated that this protein also contributes to restricting macrophage function, including production of NO and inflammatory cytokines in addition to interferon-β, in infected macrophages. Here, we showed that depletion of airway macrophages by clodronate-loaded liposomes led to developing severe viral pneumonia in recombinant C gene-knockout SeV (SeV∆C)-infected mice, but did not modulate disease severity in wild-type SeV-infected mice. Furthermore, the severe disease observed in macrophage-depleted, SeV∆C-infected mice was associated with exacerbated virus replication in the lungs, leading to severe airway inflammation and pulmonary edema, indicating lung injury. These results suggested that the antimacrophage activity of SeV C protein might play a critical role in modulating lung injury and associated diseases caused by SeV.

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