PXD043229 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Viruses antagonise expression and function of cGAMP transporters, channels and pores |
| Description | DNA sensing is a fundamental process in the immune system, including host defence against viruses. The DNA sensor cGAS synthesises 2’3’ cyclic GMP-AMP (cGAMP), a second messenger that activates STING, which subsequently induces innate immunity. cGAMP not only activates STING in the cell where it is produced but also transfers to other cells. Transporters, channels and pores including SLC19A1, the SLC46A family, P2X7, ABCC1 and volume-regulated anion channels (VRACs) release cGAMP into the extracellular space and/or import cGAMP into cells. Emerging evidence suggests these proteins are important in antiviral immunity. Here, we investigated whether viruses antagonise cGAMP transporters, channels and pores. We report that infection with multiple human viruses depleted cGAMP conduits from cells. This included herpes simplex virus 1 (HSV-1) that targeted the VRAC subunits LRRC8A and LRRC8C, as well as SLC46A2 and P2X7, for degradation. The HSV-1 protein UL56 was required and sufficient for these effects that were mediated at least partially by proteasomal turnover. UL56 thereby inhibited the cGAMP uptake via VRAC, SLC46A2 and P2X7. Taken together, we show that HSV-1 actively antagonises cGAMP transfer across the plasma membrane and propose this limits innate immunity by reducing cell-to-cell communication via the immunotransmitter cGAMP. |
| HostingRepository | PRIDE |
| AnnounceDate | 2024-10-22 |
| AnnouncementXML | Submission_2024-10-22_06:36:00.358.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | iolanda Vendrell |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
| ModificationList | phosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2023-06-23 01:02:12 | ID requested | |
| 1 | 2024-04-15 04:55:46 | announced | |
| ⏵ 2 | 2024-10-22 06:36:00 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
| submitter keyword: NA sensing |
| cGAMP |
| cGAMP transport |
| VRAC |
| LRRC8A |
| SLC46A2 |
| P2X7 |
| herpes simplex virus |
| UL56 |
Contact List
| Jan Rehwinkel |
|---|
| contact affiliation | Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK |
| contact email | jan.rehwinkel@ndm.ox.ac.uk |
| lab head | |
| iolanda Vendrell |
|---|
| contact affiliation | Target Discovery Institute, NDMRB |
| contact email | iolanda.vendrell@ndm.ox.ac.uk |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD043229
- Label: PRIDE project
- Name: Viruses antagonise expression and function of cGAMP transporters, channels and pores
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