Bortz, E.; Wu, T.; Patel, P.; Whitelegge, J.P.; Sun, R. Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection. Preprints2018, 2018090008. https://doi.org/10.20944/preprints201809.0008.v1
Bortz, E., Wu, T., Patel, P., Whitelegge, J.P., & Sun, R. (2018). Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection. Preprints. https://doi.org/10.20944/preprints201809.0008.v1
Bortz, E., Julian P. Whitelegge and Ren Sun. 2018 "Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection" Preprints. https://doi.org/10.20944/preprints201809.0008.v1
Murine herpesvirus-68 (MHV-68) productively infects the 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 9 days, as the lytic phase of infection resolved, differential BAL proteins were identified by 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 7 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 were 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 virus and IL6. Proteins and small molecules in lung oxidative stress networks therefore may provide new therapeutic targets to ameliorate respiratory virus infections.
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