| Integrity of the early secretory pathway promotes, but is not required for, severe acute respiratory syndrome coronavirus RNA synthesis and virus-induced remodeling of endoplasmic reticulum membranes. | |
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MedLine Citation:
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PMID: 19889777 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To accommodate its RNA synthesis in the infected cell, severe acute respiratory syndrome coronavirus (SARS-CoV) induces a cytoplasmic reticulovesicular network (RVN) that is derived from endoplasmic reticulum (ER) membranes. We set out to investigate how the early secretory pathway interacts with the RVN and the viral replication/transcription complex (RTC) that is anchored to it. When the secretory pathway was disrupted by brefeldin A (BFA) treatment at the start of infection, RVN formation and viral RTC activity were not blocked and continued up to 11 h postinfection, although RNA synthesis was reduced by ca. 80%. In vitro RTC assays, using membrane fractions from infected cells, demonstrated that BFA does not directly interfere with the activity of the viral RNA-synthesizing enzymes. Confocal microscopy studies showed that early secretory pathway components are not associated with SARS-CoV-induced replication sites, although our studies revealed that infection induces a remarkable redistribution of the translocon subunit Sec61alpha. Ultrastructural studies, including electron tomography, revealed that the formation of the RVN and all its previously documented features can occur in the presence of BFA, despite differences in the volume and morphology of the network. We therefore conclude that early secretory pathway proteins do not play a direct role in RVN morphogenesis or the functionality of the SARS-CoV RTC. The BFA-induced disruption of ER integrity and functionality probably affects the overall quality of the membrane scaffold that is needed to support the viral RTC and/or the availability of specific host factors, which in turn compromises viral RNA synthesis. |
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Authors:
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Kèvin Knoops; Cindy Swett-Tapia; Sjoerd H E van den Worm; Aartjan J W Te Velthuis; Abraham J Koster; A Mieke Mommaas; Eric J Snijder; Marjolein Kikkert |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-04 |
Journal Detail:
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Title: Journal of virology Volume: 84 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-23 Completed Date: 2010-01-12 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 833-46 Citation Subset: IM |
Affiliation:
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Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, LUMC E4-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brefeldin A / pharmacology Cercopithecus aethiops Electron Microscope Tomography Endoplasmic Reticulum* / metabolism, ultrastructure, virology Host-Pathogen Interactions* Humans Intracellular Membranes* / metabolism, ultrastructure, virology Microscopy, Confocal Proteins / drug effects, genetics, secretion* RNA, Viral / metabolism SARS Virus / genetics, metabolism, pathogenicity* Vero Cells / ultrastructure, virology Viral Proteins / metabolism Virus Replication |
| Chemical | |
Reg. No./Substance:
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0/Proteins; 0/RNA, Viral; 0/Viral Proteins; 20350-15-6/Brefeldin A |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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