Summary of project PR001553
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001553. The data can be accessed directly via it's Project DOI: 10.21228/M8ZB01 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001553 |
| Project DOI: | doi: 10.21228/M8ZB01 |
| Project Title: | IFN-inducible phospholipid levels govern endosomal antiviral immunity |
| Project Summary: | The interferon-induced transmembrane proteins (IFITMs) are implicated in several biological processes including antiviral defense, but their modes of action remain debated. Here, taking advantage of pseudotyped viral entry assays and replicating viruses, we uncover the requirement of host co-factors for endosomal antiviral inhibition through high-throughput proteomics and lipidomics in cellular models of IFITM restriction. Unlike plasma membrane (PM)-localized IFITM restriction that targets infectious SARS-CoV2 and other PM-fusing viral envelopes, inhibition of endosomal viral entry depends on lysines within the conserved IFITM intracellular loop. These residues recruit phosphatydilinositol-3-phosphate (PIP3) that we show here to be required for endosomal IFITM activity. We identify PIP3 as an IFN-inducible phospholipid that acts as a rheostat for endosomal antiviral immunity as its expression levels correlated with the potency of endosomal IFITM restriction and exogenous PIP3 enhanced inhibition of endocytic viruses including the recent SARS-CoV2 Omicron variant. Together, our results identify PIP3 levels as a critical regulator of endosomal IFITM restriction linking it to the Pi3K/Akt/mTORC pathway and elucidate cell-compartment specific antiviral mechanisms, informing the development of broadly acting antiviral strategies. |
| Institute: | University of Colorado Denver |
| Laboratory: | Angelo D'Alessandro |
| Last Name: | Haines |
| First Name: | Julie |
| Address: | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| Email: | julie.haines@cuanschutz.edu |
| Phone: | 3037243339 |
Summary of all studies in project PR001553
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002413 | IFN-inducible phospholipid levels govern endosomal antiviral immunity | Homo sapiens | University of Colorado Denver | MS | 2023-01-04 | 1 | 9 | Uploaded data (1.5G)* |
