Function: #efferocytosis gets a boost. IFN-I increases #apoptotic cell uptake by macrophages. This requires #ISG15; #OMA1 mitochondrial protease is dispensable for this step. ISG15 deficiency shows impaired clearance of #apoptotic cells in vivo in thymic or peritoneal challenges. #Immunosky

#ISG15 is the switch. #IFNAR signaling ISGylates mitochondrial proteins (incl. ATP synthase subunit β) to raise ATP and lower MMP. ISGylation deficient ISG15 (AA) fails to rescue; wild type ISG15 (GG) restores ATP↑ & MMP↓
#immunosky

Excessive #inflammation?
We uncover @cp-immunity.bsky.social that #IFN-I via #ISG15 in macrophages lowers #mitochondrial membrane potential, boosts #efferocytosis, and self limits #ISG amplification: a built in brake that promotes resolution. Open-access: www.cell.com/immunity/ful...
#immunosky

10 genes > entire antiviral arsenal? 🤯
Columbia researchers found a cocktail of ISG genes that fights viruses WITHOUT the inflammatory chaos. Inspired by patients who are naturally resistant to viruses. Science is wild!
Full story: buff.ly/TXO360x
#AntiviralResearch #ISG15 #ScienceIsWild

Papain‐Like Protease of SARS‐CoV‐2 Induces Intestinal Inflammation via the ISG15 Pathway: Identification of Natural Compound Inhibitors The SARS-CoV-2 papain-like protease (PLpro) is a multifunctional viral protein that facilitates viral assembly and disrupts host immune responses by removing interferon-stimulated gene 15 (ISG15) mod...

onlinelibrary.wiley.com/doi/10.1002/...

"Our results highlight the potential of targeting the #PLpro / #ISG15 interaction as a therapeutic strategy against #SARSCoV2."

Papain‐Like Protease of SARS‐CoV‐2 Induces Intestinal Inflammation via the ISG15 Pathway: Identification of Natural Compound Inhibitors The SARS-CoV-2 papain-like protease (PLpro) is a multifunctional viral protein that facilitates viral assembly and disrupts host immune responses by removing interferon-stimulated gene 15 (ISG15) mod...

onlinelibrary.wiley.com/doi/10.1002/...

"The #SARSCoV2 papain-like protease (PLpro) is a multifunctional viral protein that facilitates viral assembly and disrupts host immune responses by removing interferon-stimulated gene 15 ( #ISG15) modifications from target proteins."

#ISGylation by #ubiquitin-like #ISG15 can fight or fuel viruses ⚔️ – and is key in the #CNS too 🧠 #virology #neurobiology
➡️ doi.org/10.1002/1873-3468.70063

You know what else is #NSFfunded? Our and other lab’s work👇🏽 Thanks to a 🌎🌍🌏 collaboration, we show diversity in #ISG15 activity across 🦇

Viral tolerance enabled by a bat-specific genomic tweak Comparative genomics reveals how virus-carrying bats resist disease.

While the #ISG15 story is summarized in companion 🗞pieces, there are differences across 🦇🦇🦇, will keep many teams busy. This is one part of the story of this 🔖, happy to be part of a great #collaboration 7/7 www.nature.com/articles/d41... www.nature.com/articles/d41...

Bat genomes illuminate adaptations to viral tolerance and disease resistance - Nature A systematic analysis of 115 mammalian genomes, including 10 new bat genomes, reveals prevalent positive selection in immune genes in bats and shows key adaptations in the antiviral gene ISG15 that ai...

This is one 🗝 finding of the new 🔖: 🦇🦇🦇 show many more #immune adaptations compared to other 🐴🐈🦓🐁! So leads @ariadnamorales.bsky.social & @hillermich.bsky.social y.social reached out to @virology.bsky.social & @batresearch.bsky.social labs to test #ISG15 in 🧪 #OA 6/7

Cool paper! #ISG15 #ISGylation