Impact of SARS-CoV-2 Wuhan and Omicron Variant Proteins on Type I Interferon Response

TL;DR

This study compares how SARS-CoV-2 variants, Wuhan and Omicron, affect the body's type I interferon immune response.

Contribution

The study identifies specific viral proteins and their strain-specific roles in suppressing type I interferon responses.

Findings

Nsp1, Nsp5, Nsp14, and ORF6 are potent type I IFN inhibitors in both Wuhan and Omicron strains.

Omicron's Nsp6 and Spike proteins show enhanced IFN suppression compared to Wuhan.

Wuhan strain proteins induce a stronger type I IFN response in human endothelial cells.

Abstract

SARS-CoV-2 has demonstrated a remarkable capacity for immune evasion. While initial studies focused on the Wuhan variant and adaptive immunity, later emerging strains such as Omicron exhibit mutations that may alter their immune-modulatory properties. We performed a comprehensive review of immune evasion mechanisms associated with SARS-CoV-2 viral proteins to focus on the evolutionary dynamics of immune modulation. We systematically analyzed and compared the impact of all currently known Wuhan and Omicron SARS-CoV-2 proteins on type I interferon (IFN) responses using a dual-luciferase reporter assay carrying an interferon-inducible promoter. Results revealed that Nsp1, Nsp5, Nsp14, and ORF6 are potent type I IFN inhibitors conserved across Wuhan and Omicron strains. Notably, we identified strain-specific differences, with Nsp6 and Spike proteins exhibiting enhanced IFN suppression in Omicron, whereas the Envelope protein largely retained this function. To extend these findings, we investigated selected proteins in primary human endothelial cells and also observed strain-specific differences in immune response with higher type I IFN response in cells expressing the Wuhan strain variant, suggesting that Omicron’s adaptational mutations may contribute to a damped type I IFN response in the course of the pandemic’s trajectory.

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