Academic Journal
Coronavirus M protein disperses the trans-Golgi network and inhibits anterograde protein trafficking in the secretory pathway.
| Τίτλος: | Coronavirus M protein disperses the trans-Golgi network and inhibits anterograde protein trafficking in the secretory pathway. |
|---|---|
| Συγγραφείς: | Caddell TM; Department of Microbiology & Immunology, Dalhousie University, Halifax, Canada., Mulloy RP; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada.; Snyder Institute for Chronic Diseases and Charbonneau Institute of Cancer Research, University of Calgary, Calgary, Canada., Corcoran JA; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada.; Snyder Institute for Chronic Diseases and Charbonneau Institute of Cancer Research, University of Calgary, Calgary, Canada., Pringle ES; Department of Microbiology & Immunology, Dalhousie University, Halifax, Canada., McCormick C; Department of Microbiology & Immunology, Dalhousie University, Halifax, Canada. |
| Πηγή: | PLoS pathogens [PLoS Pathog] 2026 May 05; Vol. 22 (5), pp. e1014117. Date of Electronic Publication: 2026 May 05 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science, c2005- |
| Ιατρικοί όροι (MeSH): | trans-Golgi Network*/metabolism , trans-Golgi Network*/virology , Secretory Pathway*/physiology , SARS-CoV-2*/metabolism, Protein Transport/physiology ; Activating Transcription Factor 6/metabolism ; Endoplasmic Reticulum/metabolism ; Golgi Apparatus/metabolism ; Humans ; Animals ; Unfolded Protein Response |
| Περίληψη: | Coronaviruses (CoVs) encode a variety of transmembrane proteins that are translated and processed at the endoplasmic reticulum (ER). Three host ER resident transmembrane proteins, activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1), and PKR-like endoplasmic reticulum kinase (PERK), sense the accumulation of unfolded proteins in the ER and initiate the unfolded protein response (UPR) to maintain ER proteostasis. We observed that SARS-CoV-2 Spike broadly activated all three arms of the UPR, whereas the Membrane (M) protein selectively inhibited ATF6. ATF6 has a unique activation mechanism whereby ER stress triggers translocation to the Golgi where ATF6 is processed by resident proteases to release the ATF6-N transcription factor. We observed that M inhibited the stress-induced production of ATF6-N, suggesting that ATF6 failed to engage with Golgi proteases for processing. M also inhibited sterol regulatory element binding protein-2 (SREBP2)-mediated activation of sterol responses and stimulator of interferon response cGAMP interactor 1 (STING)-mediated activation of interferon responses, both of which are activated in the ER and require translocation to the Golgi for interactions that yield transcriptional responses. We observed that M accumulated in the cis-Golgi, and triggered dispersal of the trans-Golgi network (TGN). Using a cargo sorting assay, we determined that ER-to-Golgi cargo trafficking was intact in the presence of M, but cargo accumulated with M in the cis-Golgi and did not proceed further in the secretory pathway. We also observed aberrant cholesterol accumulation at the cis-Golgi with M, consistent with our observation of M association with detergent resistant membranes. Together, these data suggest that CoV M proteins interfere with Golgi architecture and trafficking. Because CoV egress does not require the canonical secretory pathway, this mechanism could allow the virus to selectively interfere with host responses to infection without impeding egress of nascent virions. (Copyright: © 2026 Caddell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
| Competing Interests: | The authors have declared that no competing interests exist. |
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| Substance Nomenclature: | 0 (Activating Transcription Factor 6) |
| Entry Date(s): | Date Created: 20260505 Date Completed: 20260716 Latest Revision: 20260926 |
| Update Code: | 20260926 |
| PubMed Central ID: | PMC13167032 |
| DOI: | 10.1371/journal.ppat.1014117 |
| PMID: | 42085452 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1553-7374 |
|---|---|
| DOI: | 10.1371/journal.ppat.1014117 |