SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis

Area of Science:

• Virology
• Cell Biology
• Pathology

Background:

• The COVID-19 pandemic presents a significant global health challenge.
• SARS-CoV-2 infection primarily affects the airways, leading to lung injury and cell death.
• Viral factors driving COVID-19-induced lung injury are not fully understood.

Purpose of the Study:

• To investigate the role of the SARS-CoV-2 accessory protein Orf7b in causing lung injury.
• To identify viral mechanisms contributing to cell death in COVID-19.

Main Methods:

• Screening of viral proteins to identify those mediating lung epithelial cell death.
• Overexpression of Orf7b in lung epithelial cells.
• Utilizing apoptosis and ferroptosis inhibitors.
• Investigating the role of c-Myc in Orf7b-induced cell death.
• Employing mouse models to assess lung injury.

Main Results:

• Orf7b was identified as a key viral factor inducing lung epithelial cell death.
• Orf7b overexpression triggers both apoptosis and ferroptosis in lung cells.
• Inhibiting apoptosis and ferroptosis counteracted Orf7b-induced cell death.
• Orf7b upregulates the transcription regulator c-Myc, promoting cell death pathways.
• Depleting c-Myc reduced cell death and lung injury in mouse models.

Conclusions:

• SARS-CoV-2 Orf7b plays a significant role in COVID-19-related lung cell death and injury.
• Orf7b-induced cell death involves both apoptosis and ferroptosis pathways, mediated by c-Myc.
• Orf7b represents a potential therapeutic target for mitigating COVID-19 lung pathology.