How SARS-CoV-2 Evades And Suppresses The Immune System (Part 6)

In the most recent installment of this series, I described how SARS-CoV-2 evades immune sensors by constructing a secret compartment, a double membrane vesicle, for replication and messenger RNA synthesis. But not only does the virus have to conceal their synthesis, it must camouflage the messenger RNAs themselves so they can continue to evade detection beyond the confines of the compartment. To be translated by the ribosomes, messenger RNAs must leave the compartment. If they leave unprotected, they will trigger the immune sensors.

Normally a class of innate immune receptors called Toll receptors would immediately pick up on the presence of messenger RNA that wasn’t cellular, either by recognizing the naked 5 prime end or lack of methylation, or absence of a polyadenylate 3 prime terminus. Detection by such receptors is followed by activation of secondary messages that in turn activate type-I interferons, which stimulate internal cellular pathways which destroy the RNA and that alert nearby cells to the presence of an invader. By masquerading its genome and messenger RNAs as cellular, SARS-CoV-2 produces enough virus to escape and infect other human hosts before immune defenses are fully mobilized.

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Originally published on Forbes (August 23, 2021)

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