| Cathepsin S supports acid-independent infection by some reoviruses. | |
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MedLine Citation:
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PMID: 14670972 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In murine fibroblasts, efficient proteolysis of reovirus outer capsid protein sigma3 during cell entry by virions requires the acid-dependent lysosomal cysteine protease cathepsin L. The importance of cathepsin L for infection of other cell types is unknown. Here we report that the acid-independent lysosomal cysteine protease cathepsin S mediates outer capsid processing in macrophage-like P388D cells. P388D cells supported infection by virions of strain Lang, but not strain c43. Genetic studies revealed that this difference is determined by S4, the viral gene segment that encodes sigma3. c43-derived subvirion particles that lack sigma3 replicated normally in P388D cells, suggesting that the difference in infectivity of Lang and c43 virions is at the level of sigma3 processing. Infection of P388D cells with Lang virions was inhibited by the broad spectrum cysteine protease inhibitor trans-epoxysuccinyl-l-leucylamido-(4-guanidino)butane but not by NH(4)Cl, which raises the endocytic pH and thereby inhibits acid-dependent proteases such as cathepsins L and B. Outer capsid processing and infection of P388D cells with Lang virions were also inhibited by a cathepsin S-specific inhibitor. Furthermore, in the presence of NH(4)Cl, cell lines engineered to express cathepsin S supported infection by Lang, but not c43, virions. Our results thus indicate that differences in susceptibility to cathepsin S-mediated sigma3 processing are responsible for strain differences in reovirus infection of macrophage-like P388D cells and other cathepsin S-expressing cells. Additionally, our data suggest that the acid dependence of reovirus infections of most other cell types may reflect the low pH requirement for the activities of most other lysosomal proteases rather, than some other acid-dependent aspect of cell entry. |
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Authors:
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Joseph W Golden; Jessica A Bahe; William T Lucas; Max L Nibert; Leslie A Schiff |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2003-12-11 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 279 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-03-01 Completed Date: 2004-07-06 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 8547-57 Citation Subset: IM |
Affiliation:
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Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cathepsins / metabolism* Cell Line Hydrogen-Ion Concentration Lysosomes / metabolism, virology Macrophages / enzymology, virology Mice Reoviridae / physiology* Reoviridae Infections / metabolism* Virus Replication |
| Grant Support | |
ID/Acronym/Agency:
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2T32 AI-0742/AI/NIAID NIH HHS; AI-45990/AI/NIAID NIH HHS; AI-46440/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.4.-/Cathepsins; EC 3.4.22.27/cathepsin S |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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