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Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection

1
Department of Biological Sciences, University of Alaska Anchorage, Anchorage, AK 99508, USA
2
Department of Molecular & Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
3
Center for Molecular Biology and German Cancer Research Center (DKFZ), University of Heidelberg (ZMBH), 69120 Heidelberg, Germany
4
The Pasarow Mass Spectrometry Laboratory & the Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
*
Authors to whom correspondence should be addressed.
Viruses 2018, 10(12), 670; https://doi.org/10.3390/v10120670
Received: 28 October 2018 / Revised: 15 November 2018 / Accepted: 20 November 2018 / Published: 27 November 2018
(This article belongs to the Section Animal Viruses)
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. View Full-Text
Keywords: murine herpesvirus-68; MHV-68; bronchoalveolar lavage fluid; BAL; proteomics; oxidative stress murine herpesvirus-68; MHV-68; bronchoalveolar lavage fluid; BAL; proteomics; oxidative stress
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Bortz, E.; Wu, T.-T.; Patel, P.; Whitelegge, J.P.; Sun, R. Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection. Viruses 2018, 10, 670.

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