The Role Of Nucleases In Innate Immune Escape (Part 15)

In previous installments of this series we’ve unpacked how SARS-CoV-2 is sensitive to the innate immune response, a complex assemblage of immune sensors and responders that, for high-risk Covid-19 patients especially, can mean the difference between life and death. Over a long period of time the coronavirus family has developed biochemical mechanisms that allow it to counter our innate immune defenses. Some are novel and without precedent, while others have survived generations of selective pressure due to the essential role they play in viral replication. Among the oldest in the SARS-CoV-2 genome are two viral proteins associated with the replication complex common to all coronaviruses. One is an exonuclease, nonstructural protein 14 (NSP14). The other is an endonuclease, nonstructural protein 15 (NSP15). Both are involved in critical aspects of viral replication, but also in suppression of the innate immune response. Combined, they neutralize some of the primary triggers for production of interferon and interferon-stimulated genes. Although SARS-CoV-2, like all other coronaviruses, is a positive-sense, single-stranded RNA virus, double-stranded RNA replicates are formed during the viral replication process that typically set off the innate immune response. Upon infection, receptors like RIG-I and MDA5, which induce the production of interferon and the activation of protein coding gene OAS1, detect foreign double-stranded RNA and activate their respective innate immune pathways. Unless something interferes, that is. Read full article on Forbes Originally published on Forbes (October 28, 2021)
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