Journal article
SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis
International journal of molecular sciences, Vol.25(2), p.1157
01/01/2024
DOI: 10.3390/ijms25021157
PMID: 38256231
Abstract
The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. The airway is the primary target in severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks of exposure. The viral factors that contribute to cell death and lung injury remain incompletely understood. Thus, this study investigated the role of open reading frame 7b (Orf7b), an accessory protein of the virus, in causing lung injury. In screening viral proteins, we identified Orf7b as one of the major viral factors that mediates lung epithelial cell death. Overexpression of Orf7b leads to apoptosis and ferroptosis in lung epithelial cells, and inhibitors of apoptosis and ferroptosis ablate Orf7b-induced cell death. Orf7b upregulates the transcription regulator, c-Myc, which is integral in the activation of lung cell death pathways. Depletion of c-Myc alleviates both apoptotic and ferroptotic cell deaths and lung injury in mouse models. Our study suggests a major role of Orf7b in the cell death and lung injury attributable to COVID-19 exposure, supporting it as a potential therapeutic target.
Details
- Title: Subtitle
- SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis
- Creators
- Rushikesh Deshpande - University of PittsburghWangyang Li - University of PittsburghTiao Li - University of PittsburghKristen V. Fanning - University of PittsburghZachary Clemens - University of PittsburghToru Nyunoya - University of PittsburghLianghui Zhang - University of PittsburghBerthony Deslouches - University of PittsburghAaron Barchowsky - University of PittsburghSally Wenzel - University of PittsburghJohn F. McDyer - University of PittsburghChunbin Zou - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.25(2), p.1157
- DOI
- 10.3390/ijms25021157
- PMID
- 38256231
- NLM abbreviation
- Int J Mol Sci
- ISSN
- 1661-6596
- eISSN
- 1422-0067
- Publisher
- Mdpi
- Number of pages
- 17
- Grant note
- National Institutes of Health R01; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2024
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985214101802771
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