Figure 5.

Control of virus replication diminished fibrogenesis in MHV68 IFN-γR^−/− infected mice. (A) NIH3T3 cells stably transfected with a fibronectin reporter were cultured for 24 hours in the presence of bronchoalveolar lavage (BAL) fluid from mock and virus-infected animals treated with saline solution (SS) or antiviral (AV). Afterward, the cells were harvested and fibronectin gene transcription was measured by luminescence (n = 4 per group). MHV68 infection stimulates gene transcription of a reporter under control of the fibronectin promoter. AV treatment significantly diminished fibronectin transcription. (B) Western blot analysis for the latent and active forms of transforming growth factor (TGF)-β in BAL fluid samples collected on Day 120. The blot was stripped and reprobed with an anti-surfactant A (SP-A) antibody to normalize expression of latent (open columns) and active (solid columns) TGF-β. Decreased levels of active TGF-β were found in infected mice treated with the antiviral agent. (C) Gelatin zymography of BAL fluid samples from mock and MHV68-infected animals at the indicated times points after infection. High gelatinolytic activity was observed in samples from infected mice compared with mock animals and infected animals treated with antiviral agent. Purified matrix metalloproteinase (MMP)–2 and MMP-9 were used to identify zymography bands in the samples from virus-infected animals treated with SS.