STING orchestrates EV-D68 replication and immunometabolism within viral-induced replication organelles

Triantafilou, Kathy ORCID: https://orcid.org/0000-0002-7473-6278, Szomolay, Barbara ORCID: https://orcid.org/0000-0002-5375-5533, Shepherd, Mark William, Ramanjulu, Joshi and Triantafilou, Martha ORCID: https://orcid.org/0000-0002-8489-2602 2024. STING orchestrates EV-D68 replication and immunometabolism within viral-induced replication organelles. Viruses 16 (10) , 1541. 10.3390/v16101541

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Abstract

Some respiratory viruses, such as Human Rhinovirus, SARS-CoV-2, and Enterovirus D-68 (EV-D68), share the feature of hijacking host lipids in order to generate specialised replication organelles (ROs) with unique lipid compositions to enable viral replication. We have recently uncovered a novel non-canonical function of the stimulator of interferon genes (STING) pathway, as a critical factor in the formation of ROs in response to HRV infection. The STING pathway is the main DNA virus sensing system of the innate immune system controlling the type I IFN machinery. Although it is well-characterised as part of the DNA sensor machinery, the STING function in RNA viral infections is largely unexplored. In the current study, we investigated whether other RO-forming RNA viruses, such as EV-D68 and SARS-CoV-2, can also utilise STING for their replication. Using genetic and pharmacological inhibition, we demonstrate that STING is hijacked by these viruses and is utilised as part of the viral replication machinery. STING also co-localises with glycolytic enzymes needed to fuel the energy for replication. The inhibition of STING leads to the modulation of glucose metabolism in EV-D68-infected cells, suggesting that it might also manipulate immunometabolism. Therefore, for RO-generating RNA viruses, STING seems to have non-canonical functions in membrane lipid re-modelling, and the formation of replication vesicles, as well as immunometabolism.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	MDPI
Date of First Compliant Deposit:	16 October 2024
Date of Acceptance:	19 September 2024
Last Modified:	16 Oct 2024 14:30
URI:	https://orca.cardiff.ac.uk/id/eprint/172952

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