| Chikungunya virus mobilizes the apoptotic machinery to invade host cell defenses. | |
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MedLine Citation:
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PMID: 20881210 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chikungunya virus (CHIKV) surprised medical workers by a massive outbreak in the Indian Ocean region, reaching Europe in 2007, with exceptional pathologies in infants and elderly patients. Although CHIKV was recently shown to persist in myoblasts, monocytes, and macrophages, we argued that robust antiviral mechanisms, including apoptosis, are essential to ward off the virus. Herein, we tested the capacity of CHIKV to mobilize the apoptotic machinery in HeLa cells as well as primary fibroblasts, making use of several inhibitors of caspases, cell blebbing, and engulfment of the apoptotic blebs by neighboring cells. CHIKV triggered apoptosis through intrinsic and extrinsic pathways. Bystander apoptosis was also evidenced in neighboring cells in a caspase-8-dependent manner. Remarkably, by hiding in apoptotic blebs, CHIKV was able to infect neighboring cells. In HeLa cells, these events were inhibited specifically by zVAD-fmk and DEVD-cho (caspase inhibitors), blebbistatin, Y-27632 (ROCK inhibitor), and genistein, annexin V, and cytochalasin B (inhibitors of blebbing and engulfment). These CHIKV-apoptotic blebs were also capable of infecting macrophages (primary cultures, MM6- and THP1-PMA differentiated cells) otherwise refractory to infection by CHIKV alone. Remarkably, viral replication in macrophages did not yield a proinflammatory response. We describe a novel infectious mechanism by which CHIKV invades host cells and escapes the host response. |
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Authors:
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Pascale Krejbich-Trotot; Melanie Denizot; Jean-Jacques Hoarau; Marie-Christine Jaffar-Bandjee; Trina Das; Philippe Gasque |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-29 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 25 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-05 Completed Date: 2011-03-08 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 314-25 Citation Subset: IM |
Affiliation:
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GRI/IRG Immunopathology and Infection Research Grouping, University of La Réunion, CYROI, 2 rue Maxime Rivière, 97491, Ste Clotilde, Reunion. pascale.krejbich-trotot@chr-reunion.fr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alphavirus Infections
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virology Amides / pharmacology Amino Acid Chloromethyl Ketones / pharmacology Animals Apoptosis / drug effects, physiology* Blotting, Western Bystander Effect / drug effects Caspase 8 / antagonists & inhibitors, metabolism Cell Line Cell Survival / drug effects Cells, Cultured Cercopithecus aethiops Chikungunya virus / physiology* Cytopathogenic Effect, Viral / drug effects Fibroblasts / cytology, metabolism, virology* Genistein / pharmacology HeLa Cells Heterocyclic Compounds with 4 or More Rings / pharmacology Host-Pathogen Interactions / drug effects Humans Macrophages / cytology, metabolism, virology* Oligopeptides / pharmacology Pyridines / pharmacology Vero Cells bcl-2-Associated X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Amides; 0/Amino Acid Chloromethyl Ketones; 0/Heterocyclic Compounds with 4 or More Rings; 0/Oligopeptides; 0/Pyridines; 0/aspartyl-glutamyl-valyl-aspartal; 0/bcl-2-Associated X Protein; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 0/blebbistatin; 138381-45-0/Y 27632; 446-72-0/Genistein; EC 3.4.22.-/Caspase 8 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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