Expression of hepatitis C virus NS5A natural mutants in a hepatocytic cell line inhibits the antiviral effect of interferon in a PKR-independent manner
The impact of hepatitis C virus NS5A protein mutations on interferon alfa (IFN-α) signaling pathway, cell proliferation, and viability is an important issue that is still under debate. We have therefore combined transient and stable expression in a human hepatocytic cell line (Huh7) of 3 full-length...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2001-06, Vol.33 (6), p.1503-1511 |
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| container_title | Hepatology (Baltimore, Md.) |
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| creator | Podevin, Philippe Sabile, Abdelmajid Gajardo, Rodrigo Delhem, Nadira Abadie, Annie Lozach, Pierre-Yves Beretta, Laura Bréchot, Christian |
| description | The impact of hepatitis C virus NS5A protein mutations on interferon alfa (IFN-α) signaling pathway, cell proliferation, and viability is an important issue that is still under debate. We have therefore combined transient and stable expression in a human hepatocytic cell line (Huh7) of 3 full-length NS5A sequences, isolated from patients with or without response to IFN-α therapy. Expression of all 3 NS5A-reduced IFN-α global antiviral activity on both vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) replication. We did not show, however, an effect of these 3 NS5A proteins on double-stranded RNA–dependent kinase (PKR) expression and activity as well as colocalization and coimmunoprecipitation between NS5A and PKR. We also failed to show an effect of the 3 NS5A mutants tested on cell proliferation and viability. Overall, our results support an important role of NS5A in controlling IFN-α antiviral activity; they show, however, that PKR-independent mechanisms are implicated, at least in liver-derived cells. (HEPATOLOGY 2001;33:1503-1511.) |
| doi_str_mv | 10.1053/jhep.2001.24749 |
| format | Article |
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We have therefore combined transient and stable expression in a human hepatocytic cell line (Huh7) of 3 full-length NS5A sequences, isolated from patients with or without response to IFN-α therapy. Expression of all 3 NS5A-reduced IFN-α global antiviral activity on both vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) replication. We did not show, however, an effect of these 3 NS5A proteins on double-stranded RNA–dependent kinase (PKR) expression and activity as well as colocalization and coimmunoprecipitation between NS5A and PKR. We also failed to show an effect of the 3 NS5A mutants tested on cell proliferation and viability. Overall, our results support an important role of NS5A in controlling IFN-α antiviral activity; they show, however, that PKR-independent mechanisms are implicated, at least in liver-derived cells. (HEPATOLOGY 2001;33:1503-1511.)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1053/jhep.2001.24749</identifier><identifier>PMID: 11391540</identifier><language>eng</language><publisher>Philadelphia, PA: Elsevier Inc</publisher><subject>2',5'-Oligoadenylate Synthetase - genetics ; 3T3 Cells ; Amino Acid Sequence - genetics ; Animals ; Antiviral Agents - antagonists & inhibitors ; Cell Division - physiology ; Cell Line ; Cell Survival - physiology ; eIF-2 Kinase - genetics ; eIF-2 Kinase - physiology ; Gene Expression ; GTP-Binding Proteins ; Hepatocytes - physiology ; Humans ; Interferon-alpha - antagonists & inhibitors ; Life Sciences ; Mice ; Microbiology and Parasitology ; Molecular Sequence Data ; Mutation - genetics ; Myxovirus Resistance Proteins ; Precipitin Tests ; Proteins - genetics ; Rats ; Tissue Distribution ; Viral Nonstructural Proteins - genetics ; Viral Nonstructural Proteins - metabolism ; Virology</subject><ispartof>Hepatology (Baltimore, Md.), 2001-06, Vol.33 (6), p.1503-1511</ispartof><rights>2001 The American Association for the Study of Liver Diseases</rights><rights>Copyright © 2001 American Association for the Study of Liver Diseases</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4681-99d1dd8922c0a6db3bfc6b3d71c5b2168d57dde2b22b0de9b194a29c4c434e273</citedby><orcidid>0000-0002-9966-1452</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1053%2Fjhep.2001.24749$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1053%2Fjhep.2001.24749$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11391540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.inrae.fr/hal-03331586$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Podevin, Philippe</creatorcontrib><creatorcontrib>Sabile, Abdelmajid</creatorcontrib><creatorcontrib>Gajardo, Rodrigo</creatorcontrib><creatorcontrib>Delhem, Nadira</creatorcontrib><creatorcontrib>Abadie, Annie</creatorcontrib><creatorcontrib>Lozach, Pierre-Yves</creatorcontrib><creatorcontrib>Beretta, Laura</creatorcontrib><creatorcontrib>Bréchot, Christian</creatorcontrib><title>Expression of hepatitis C virus NS5A natural mutants in a hepatocytic cell line inhibits the antiviral effect of interferon in a PKR-independent manner</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>The impact of hepatitis C virus NS5A protein mutations on interferon alfa (IFN-α) signaling pathway, cell proliferation, and viability is an important issue that is still under debate. We have therefore combined transient and stable expression in a human hepatocytic cell line (Huh7) of 3 full-length NS5A sequences, isolated from patients with or without response to IFN-α therapy. Expression of all 3 NS5A-reduced IFN-α global antiviral activity on both vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) replication. We did not show, however, an effect of these 3 NS5A proteins on double-stranded RNA–dependent kinase (PKR) expression and activity as well as colocalization and coimmunoprecipitation between NS5A and PKR. We also failed to show an effect of the 3 NS5A mutants tested on cell proliferation and viability. Overall, our results support an important role of NS5A in controlling IFN-α antiviral activity; they show, however, that PKR-independent mechanisms are implicated, at least in liver-derived cells. (HEPATOLOGY 2001;33:1503-1511.)</description><subject>2',5'-Oligoadenylate Synthetase - genetics</subject><subject>3T3 Cells</subject><subject>Amino Acid Sequence - genetics</subject><subject>Animals</subject><subject>Antiviral Agents - antagonists & inhibitors</subject><subject>Cell Division - physiology</subject><subject>Cell Line</subject><subject>Cell Survival - physiology</subject><subject>eIF-2 Kinase - genetics</subject><subject>eIF-2 Kinase - physiology</subject><subject>Gene Expression</subject><subject>GTP-Binding Proteins</subject><subject>Hepatocytes - physiology</subject><subject>Humans</subject><subject>Interferon-alpha - antagonists & inhibitors</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Microbiology and Parasitology</subject><subject>Molecular Sequence Data</subject><subject>Mutation - genetics</subject><subject>Myxovirus Resistance Proteins</subject><subject>Precipitin Tests</subject><subject>Proteins - genetics</subject><subject>Rats</subject><subject>Tissue Distribution</subject><subject>Viral Nonstructural Proteins - genetics</subject><subject>Viral Nonstructural Proteins - metabolism</subject><subject>Virology</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuOEzEQRS0EYsLAmh3ylkVn_OiXl1EUCCKCEY-15barlRp13JHtZMiX8Lu4p0fMCrGxpapzb5XqEvKWsyVnlby528NxKRjjS1E2pXpGFrwSTSFlxZ6TBRMNKxSX6oq8ivGOMaZK0b4kVzzXeFWyBfm9-XUMECOOno49zXYmYcJI1_SM4RTpl-_VinqTTsEM9HBKxqdI0VMzs6O9JLTUwjDQAT3k1h47zEzaA80wZpushL4Hm6YR6BOEHkIe-GBz-_lbgd7BEfLjEz0Y7yG8Ji96M0R48_hfk58fNj_W22L39eOn9WpX2LJueaGU4861SgjLTO062fW27qRruK06wevWVY1zIDohOuZAdVyVRihb2lKWIBp5Td7Pvnsz6GPAgwkXPRrU29VOTzUmpeRVW595Zm9m1oYxxgD9XwFneopDT3HoKQ79EEdWvJsVx1N3APfEP94_A2oG7nGAy__89HZzW_G8EasFf9JCvs8ZIehoEbwFhyHfWrsR_7nYH6IVrJ8</recordid><startdate>200106</startdate><enddate>200106</enddate><creator>Podevin, Philippe</creator><creator>Sabile, Abdelmajid</creator><creator>Gajardo, Rodrigo</creator><creator>Delhem, Nadira</creator><creator>Abadie, Annie</creator><creator>Lozach, Pierre-Yves</creator><creator>Beretta, Laura</creator><creator>Bréchot, Christian</creator><general>Elsevier Inc</general><general>W.B. 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We have therefore combined transient and stable expression in a human hepatocytic cell line (Huh7) of 3 full-length NS5A sequences, isolated from patients with or without response to IFN-α therapy. Expression of all 3 NS5A-reduced IFN-α global antiviral activity on both vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) replication. We did not show, however, an effect of these 3 NS5A proteins on double-stranded RNA–dependent kinase (PKR) expression and activity as well as colocalization and coimmunoprecipitation between NS5A and PKR. We also failed to show an effect of the 3 NS5A mutants tested on cell proliferation and viability. Overall, our results support an important role of NS5A in controlling IFN-α antiviral activity; they show, however, that PKR-independent mechanisms are implicated, at least in liver-derived cells. 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| identifier | ISSN: 0270-9139 |
| ispartof | Hepatology (Baltimore, Md.), 2001-06, Vol.33 (6), p.1503-1511 |
| issn | 0270-9139 1527-3350 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 2',5'-Oligoadenylate Synthetase - genetics 3T3 Cells Amino Acid Sequence - genetics Animals Antiviral Agents - antagonists & inhibitors Cell Division - physiology Cell Line Cell Survival - physiology eIF-2 Kinase - genetics eIF-2 Kinase - physiology Gene Expression GTP-Binding Proteins Hepatocytes - physiology Humans Interferon-alpha - antagonists & inhibitors Life Sciences Mice Microbiology and Parasitology Molecular Sequence Data Mutation - genetics Myxovirus Resistance Proteins Precipitin Tests Proteins - genetics Rats Tissue Distribution Viral Nonstructural Proteins - genetics Viral Nonstructural Proteins - metabolism Virology |
| title | Expression of hepatitis C virus NS5A natural mutants in a hepatocytic cell line inhibits the antiviral effect of interferon in a PKR-independent manner |
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