| First Author | Ashley SL | Year | 2014 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 307 |
| Issue | 3 | Pages | L219-30 |
| PubMed ID | 24879051 | Mgi Jnum | J:221712 |
| Mgi Id | MGI:5641405 | Doi | 10.1152/ajplung.00300.2013 |
| Citation | Ashley SL, et al. (2014) gamma-Herpes virus-68, but not Pseudomonas aeruginosa or influenza A (H1N1), exacerbates established murine lung fibrosis. Am J Physiol Lung Cell Mol Physiol 307(3):L219-30 |
| abstractText | Patients with idiopathic pulmonary fibrosis (IPF) often do worse following infection, but the cause of the decline is not fully understood. We previously demonstrated that infection with a murine gamma herpes virus (gammaHV-68) could exacerbate established lung fibrosis following administration of fluorescein isothiocyanate (McMillan et al. Am J Respir Crit Care Med 177: 771-780, 2008). In the present study, we anesthetized mice and injected saline or bleomycin intratracheally on day 0. On day 14, mice were anesthetized again and infected with either a Gram-negative bacteria (Pseudomonas aeruginosa), or with H1N1 or gammaHV-68 viruses. Measurements were then made on days 15, 21, or 35. We demonstrate that infection with P. aeruginosa does not exacerbate extracellular matrix deposition post-bleomycin. Furthermore, fibrotic mice are effectively able to clear P. aeruginosa infection. In contrast, bleomycin-treated mice develop worse lung fibrosis when infected with gammaHV-68, but not when infected with H1N1. The differential ability of gammaHV-68 to cause increased collagen deposition could not be explained by differences in inflammatory cell recruitment or whole lung chemokine and cytokine responses. Alveolar epithelial cells from gammaHV-68-infected mice displayed increased expression of TGFbeta receptor 1, increased SMAD3 phosphorylation, and evidence of apoptosis measured by cleaved poly-ADP ribose polymerase (PARP). The ability of gammaHV-68 to augment fibrosis required the ability of the virus to reactivate from latency. This property appears unique to gammaHV-68, as the beta-herpes virus, cytomegalovirus, did not have the same effect. |
