Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection
Bortz, E.; Wu, T.-T.; Patel, P.; Whitelegge, J.P.; Sun, R.
ISSN/ISBN: 1999-4915 PMID: 30486363 DOI: 10.3390/v10120670
Murine herpesvirus-68 (MHV-68) productively infects mouse lungs, exhibiting a complex pathology characteristic of both acute viral infections and chronic respiratory diseases. We sought to discover proteins differentially expressed in bronchoalveolar lavage (BAL) from mice infected with MHV-68. Mice were infected intranasally with MHV-68. After nine days, as the lytic phase of infection resolved, differential BAL proteins were identified by two-dimensional (2D) electrophoresis and mass spectrometry. Of 23 unique proteins, acute phase proteins, vitamin A transport, and oxidative stress response factors Pdx6 and EC-SOD (Sod3) were enriched. Correspondingly, iNOS2 was induced in lung tissue by seven days post-infection. Oxidative stress was partly a direct result of MHV-68 infection, as reactive oxygen species (ROS) were induced in cultured murine NIH3T3 fibroblasts and human lung A549 cells infected with MHV-68. Finally, mice infected with a recombinant MHV-68 co-expressing inflammatory cytokine murine interleukin 6 (IL6) showed exacerbated oxidative stress and soluble type I collagen characteristic of tissue recovery. Thus, oxidative stress appears to be a salient feature of MHV-68 pathogenesis, in part caused by lytic replication of the virus and IL6. Proteins and small molecules in lung oxidative stress networks therefore may provide new therapeutic targets to ameliorate respiratory virus infections.