How SARS-CoV-2 Evades And Suppresses The Immune System (Part 7)

Part six of this series delved into the details of how SARS-CoV-2 masquerades its viral messenger RNAs as cellular messenger RNAs. Now I will take a moment to zoom out and introduce a framework that will guide us through the next few installments: specific vs. nonspecific SARS-CoV-2 immune suppression.

To recap, SARS-CoV-2 encodes many proteins in its genome that modify and suppress the immune system. New variants appear to improve upon these existing capabilities, allowing the virus to replicate to high concentrations without drawing the attention of cellular immune sensors. The primary objective is downregulation of interferon and interferon-stimulated genes.

SARS-CoV-2 has nonstructural proteins (NSPs) and accessory genes, including open reading frames (Orfs), that contribute collectively to this effort. Like Swiss army knives, the viral proteins of SARS-CoV-2 are multifunctional, with many performing several highly specific tasks. NSP3 alone encodes seven distinct functional domains, including protease cleavage, de-ubiquitination, de-ADP-ribosylation, and autophagy modulation.

All the virus’ mechanisms of immune suppression can be generally described as specific or nonspecific. Nonspecific refers to viral proteins that block entire pathways, such as export of viral proteins from the cell. Specific pathways are those that interfere with one or two cellular functions of immunoregulatory pathways only.

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Originally published on Forbes (August 24, 2021)

© William A. Haseltine, PhD. All Rights Reserved.