Proteomics of bronchoalveolar lavage fluid reveals a lung oxidative stress response in murine herpesvirus-68 infection
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...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
27 November 2018
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| In: |
Viruses
Year: 2018, Volume: 10, Issue: 12 |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v10120670 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/v10120670 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1999-4915/10/12/670 |
| Author Notes: | Eric Bortz, Ting-Ting Wu, Parthive Patel, Julian P. Whitelegge and Ren Sun |
| Summary: | 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. |
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| Item Description: | Gesehen am 30.03.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v10120670 |