IMMUNOLOGY2026™ Conference Recordings For Attendees-Reversible ISG15 conjugation regulates antiviral innate immunity and intracellular metabolism

Reversible ISG15 conjugation regulates antiviral innate immunity and intracellular metabolism

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Video Summary

The speaker described how SARS-CoV-2 uses its papain-like protease (PLpro/NSP3) to remove ISG15-like modifications from host proteins, helping the virus evade immunity and reshape cell metabolism. They engineered a mutant virus that kept deubiquitinating activity but lost deISGylating activity. This mutant was attenuated in mice and triggered stronger interferon and antiviral gene responses, showing that PLpro deISGylation normally suppresses innate immunity in a cell-type-dependent way.<br /><br />They also found that PLpro alters host metabolism by targeting key glycolysis and pentose phosphate pathway enzymes, especially aldolase A and PRDX1. DeISGylation disrupted these enzymes’ oligomerization and activity, leading to impaired glycolysis, reduced antioxidant defense, increased oxidative stress, and less favorable conditions for viral replication. Overall, the study shows PLpro-driven deISGylation supports both immune evasion and metabolic reprogramming to promote SARS-CoV-2 infection.

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Date April 17, 2026 9:54 AM - 10:09 AM

Room 253

Session Major Symposium C: Epigenetic Modifiers as Drivers of Immune Function

Speaker Junji Zhu

Track Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

Year 2026

Keywords

SARS-CoV-2 PLpro

deISGylation

innate immunity evasion

host metabolism reprogramming

glycolysis and oxidative stress

April 17, 2026 9:54 AM - 10:09 AM

253

Major Symposium C: Epigenetic Modifiers as Drivers of Immune Function

Junji Zhu

Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

2026