SARS-CoV-2 S, M, and E Structural Glycoproteins Differentially Modulate Endoplasmic Reticulum Stress Responses.

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Hepatitis C virus (HCV) E1E2 glycoprotein disrupts NF-κB activation and upregulates endoplasmic reticulum (ER) stress.
• Understanding how other viral proteins modulate host cell pathways is crucial for disease research.

Purpose of the Study:

• To investigate the impact of SARS-CoV-2 structural proteins (S, M, E, N) on HIV-1 long-terminal repeat (LTR) activity.
• To analyze gene expression changes associated with SARS-CoV-2 structural protein expression and their relation to cellular stress pathways.

Main Methods:

• Utilized pseudo-typed viral particles (PVP) to create cell lines expressing SARS-CoV-2 structural proteins.
• Performed differential gene expression analysis (DGEA) on cells expressing S, M, E, or N proteins.
• Assessed modulation of HIV-1 LTR activity and NF-κB signaling.

Main Results:

• SARS-CoV-2 S, M, and E proteins, but not N, dose-dependently downmodulated HIV-1 LTR activity.
• The Wuhan S strain showed the highest effect, with decreasing impact from subsequent variants (Omicron weakest).
• Upregulation of interferon-stimulated genes (ISGs) and heat shock protein (HSP) genes was observed, alongside altered transcription factor patterns (SP1, MAVS).

Conclusions:

• SARS-CoV-2 structural proteins, particularly envelope glycoproteins, can activate ER stress pathways and disrupt NF-κB signaling.
• SARS-CoV-2 infection modulates cellular pathways, affecting physiological responses in infected cells.
• Gene expression changes indicate a broad cellular response to SARS-CoV-2 structural protein expression.