Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome entry site (IRES) dependent translation in vitro
The internal ribosome entry site (IRES) of hepatitis C virus (HCV) which governs the initiation of protein synthesis from viral RNA represents an ideal target for antisense approaches. Using an original bicistronic plasmid, we first established that sequence and translational activity of HCV IRESs c...
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| Veröffentlicht in: | Antiviral research 2008-12, Vol.80 (3), p.280-287 |
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| creator | Alotte, Christine Martin, Amaury Caldarelli, Sergio A. Di Giorgio, Audrey Condom, Roger Zoulim, Fabien Durantel, David Hantz, Olivier |
| description | The internal ribosome entry site (IRES) of hepatitis C virus (HCV) which governs the initiation of protein synthesis from viral RNA represents an ideal target for antisense approaches. Using an original bicistronic plasmid, we first established that sequence and translational activity of HCV IRESs cloned from six patients, whether responders or not to combination therapy, were conserved. We then tested the hypothesis that antisense molecules, i.e. short peptide nucleic acids (PNA), could inhibit HCV translation by binding to the highly conserved IIId or IV loop regions of the IRES. Five 6–10
mer PNAs were designed. They strongly inhibit HCV IRES-driven translation in a rabbit reticulocyte lysate assay. This inhibition was highly specific since corresponding PNAs with only one mismatch were inactive. Short phosphorothioate oligonucleotides of same sequence were unable to inhibit HCV translation. PNA molecule was shown to have anti-HCV activity in Huh-7.5 cells when electroporated with a full-length HCV genome construct. Using oligonucleotide as carrier, PNA was also transfected in HCV replicon-harboring cells and in JFH1 infected Huh-7.5 cells. |
| doi_str_mv | 10.1016/j.antiviral.2008.06.011 |
| format | Article |
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mer PNAs were designed. They strongly inhibit HCV IRES-driven translation in a rabbit reticulocyte lysate assay. This inhibition was highly specific since corresponding PNAs with only one mismatch were inactive. Short phosphorothioate oligonucleotides of same sequence were unable to inhibit HCV translation. PNA molecule was shown to have anti-HCV activity in Huh-7.5 cells when electroporated with a full-length HCV genome construct. Using oligonucleotide as carrier, PNA was also transfected in HCV replicon-harboring cells and in JFH1 infected Huh-7.5 cells.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2008.06.011</identifier><identifier>PMID: 18625270</identifier><identifier>CODEN: ARSRDR</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>5' Untranslated Regions ; Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antisense ; Antiviral agents ; Base Sequence ; Biological and medical sciences ; Cell Line ; DNA, Antisense - chemistry ; DNA, Antisense - genetics ; DNA, Antisense - pharmacology ; Down-Regulation - drug effects ; Hepacivirus - chemistry ; Hepacivirus - drug effects ; Hepacivirus - genetics ; Hepacivirus - metabolism ; Hepatitis C - drug therapy ; Hepatitis C - virology ; Hepatitis C virus ; Human viral diseases ; Humans ; Infectious diseases ; IRES ; JFH1 strain ; Medical sciences ; Molecular Sequence Data ; Peptide nucleic acid ; Peptide Nucleic Acids - chemistry ; Peptide Nucleic Acids - genetics ; Peptide Nucleic Acids - pharmacology ; Pharmacology. Drug treatments ; PNA ; Protein Biosynthesis - drug effects ; Rabbits ; Reticulocytes - metabolism ; Ribosomes - drug effects ; Ribosomes - genetics ; Ribosomes - metabolism ; Viral diseases ; Viral hepatitis</subject><ispartof>Antiviral research, 2008-12, Vol.80 (3), p.280-287</ispartof><rights>2008 Elsevier B.V.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-41fb9a9a8b0eb8941353167abd465266a1deeaa3f086f804e20e647cfc87f6b93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0166354208003306$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20952705$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18625270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alotte, Christine</creatorcontrib><creatorcontrib>Martin, Amaury</creatorcontrib><creatorcontrib>Caldarelli, Sergio A.</creatorcontrib><creatorcontrib>Di Giorgio, Audrey</creatorcontrib><creatorcontrib>Condom, Roger</creatorcontrib><creatorcontrib>Zoulim, Fabien</creatorcontrib><creatorcontrib>Durantel, David</creatorcontrib><creatorcontrib>Hantz, Olivier</creatorcontrib><title>Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome entry site (IRES) dependent translation in vitro</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>The internal ribosome entry site (IRES) of hepatitis C virus (HCV) which governs the initiation of protein synthesis from viral RNA represents an ideal target for antisense approaches. Using an original bicistronic plasmid, we first established that sequence and translational activity of HCV IRESs cloned from six patients, whether responders or not to combination therapy, were conserved. We then tested the hypothesis that antisense molecules, i.e. short peptide nucleic acids (PNA), could inhibit HCV translation by binding to the highly conserved IIId or IV loop regions of the IRES. Five 6–10
mer PNAs were designed. They strongly inhibit HCV IRES-driven translation in a rabbit reticulocyte lysate assay. This inhibition was highly specific since corresponding PNAs with only one mismatch were inactive. Short phosphorothioate oligonucleotides of same sequence were unable to inhibit HCV translation. PNA molecule was shown to have anti-HCV activity in Huh-7.5 cells when electroporated with a full-length HCV genome construct. Using oligonucleotide as carrier, PNA was also transfected in HCV replicon-harboring cells and in JFH1 infected Huh-7.5 cells.</description><subject>5' Untranslated Regions</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antisense</subject><subject>Antiviral agents</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>DNA, Antisense - chemistry</subject><subject>DNA, Antisense - genetics</subject><subject>DNA, Antisense - pharmacology</subject><subject>Down-Regulation - drug effects</subject><subject>Hepacivirus - chemistry</subject><subject>Hepacivirus - drug effects</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - metabolism</subject><subject>Hepatitis C - drug therapy</subject><subject>Hepatitis C - virology</subject><subject>Hepatitis C virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>IRES</subject><subject>JFH1 strain</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Peptide nucleic acid</subject><subject>Peptide Nucleic Acids - chemistry</subject><subject>Peptide Nucleic Acids - genetics</subject><subject>Peptide Nucleic Acids - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>PNA</subject><subject>Protein Biosynthesis - drug effects</subject><subject>Rabbits</subject><subject>Reticulocytes - metabolism</subject><subject>Ribosomes - drug effects</subject><subject>Ribosomes - genetics</subject><subject>Ribosomes - metabolism</subject><subject>Viral diseases</subject><subject>Viral hepatitis</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EokPhFcAbqnaRYOfHP8vRqLSVKkAU1pbj3GjuKOME26nUDc-ORzMqy64s2d8517ofIZ84Kznj4suutD7hIwY7lhVjqmSiZJy_IiuuZFVopsVrssqkKOq2qc7Iuxh3jDEhtXpLzrgSVVtJtiJ_H7ZTSHSGOWEP1C9uBHTUOuwjvfzxbX1F0W-xw0S3MNuECSPd0Dx5ifklQfB2pAG7KU57oOBTeKIRE9DLu5_XD1e0hxl8n-9pCtbHMVdMPidzRQrTe_JmsGOED6fznPz-ev1rc1vcf7-526zvC9fULBUNHzpttVUdg07phtdtzYW0Xd-IthLC8h7A2npgSgyKNVAxEI10g1NyEJ2uz8nFsXcO058FYjJ7jA7G0XqYlmiEVlxqrl4EuZaiFlxmUB5BF6YYAwxmDri34clwZg6OzM48OzIHR4YJkx3l5MfTiKXbQ_8_d5KSgc8nwEZnxyHvzWF85iqmD1ibufWRg7y5R4RgokPwDnoM4JLpJ3zxM_8Ahmq1Ng</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Alotte, Christine</creator><creator>Martin, Amaury</creator><creator>Caldarelli, Sergio A.</creator><creator>Di Giorgio, Audrey</creator><creator>Condom, Roger</creator><creator>Zoulim, Fabien</creator><creator>Durantel, David</creator><creator>Hantz, Olivier</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T7</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20081201</creationdate><title>Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome entry site (IRES) dependent translation in vitro</title><author>Alotte, Christine ; Martin, Amaury ; Caldarelli, Sergio A. ; Di Giorgio, Audrey ; Condom, Roger ; Zoulim, Fabien ; Durantel, David ; Hantz, Olivier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-41fb9a9a8b0eb8941353167abd465266a1deeaa3f086f804e20e647cfc87f6b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>5' Untranslated Regions</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antisense</topic><topic>Antiviral agents</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>DNA, Antisense - chemistry</topic><topic>DNA, Antisense - genetics</topic><topic>DNA, Antisense - pharmacology</topic><topic>Down-Regulation - drug effects</topic><topic>Hepacivirus - chemistry</topic><topic>Hepacivirus - drug effects</topic><topic>Hepacivirus - genetics</topic><topic>Hepacivirus - metabolism</topic><topic>Hepatitis C - drug therapy</topic><topic>Hepatitis C - virology</topic><topic>Hepatitis C virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>IRES</topic><topic>JFH1 strain</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Peptide nucleic acid</topic><topic>Peptide Nucleic Acids - chemistry</topic><topic>Peptide Nucleic Acids - genetics</topic><topic>Peptide Nucleic Acids - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>PNA</topic><topic>Protein Biosynthesis - drug effects</topic><topic>Rabbits</topic><topic>Reticulocytes - metabolism</topic><topic>Ribosomes - drug effects</topic><topic>Ribosomes - genetics</topic><topic>Ribosomes - metabolism</topic><topic>Viral diseases</topic><topic>Viral hepatitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alotte, Christine</creatorcontrib><creatorcontrib>Martin, Amaury</creatorcontrib><creatorcontrib>Caldarelli, Sergio A.</creatorcontrib><creatorcontrib>Di Giorgio, Audrey</creatorcontrib><creatorcontrib>Condom, Roger</creatorcontrib><creatorcontrib>Zoulim, Fabien</creatorcontrib><creatorcontrib>Durantel, David</creatorcontrib><creatorcontrib>Hantz, Olivier</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Antiviral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alotte, Christine</au><au>Martin, Amaury</au><au>Caldarelli, Sergio A.</au><au>Di Giorgio, Audrey</au><au>Condom, Roger</au><au>Zoulim, Fabien</au><au>Durantel, David</au><au>Hantz, Olivier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome entry site (IRES) dependent translation in vitro</atitle><jtitle>Antiviral research</jtitle><addtitle>Antiviral Res</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>80</volume><issue>3</issue><spage>280</spage><epage>287</epage><pages>280-287</pages><issn>0166-3542</issn><eissn>1872-9096</eissn><coden>ARSRDR</coden><abstract>The internal ribosome entry site (IRES) of hepatitis C virus (HCV) which governs the initiation of protein synthesis from viral RNA represents an ideal target for antisense approaches. Using an original bicistronic plasmid, we first established that sequence and translational activity of HCV IRESs cloned from six patients, whether responders or not to combination therapy, were conserved. We then tested the hypothesis that antisense molecules, i.e. short peptide nucleic acids (PNA), could inhibit HCV translation by binding to the highly conserved IIId or IV loop regions of the IRES. Five 6–10
mer PNAs were designed. They strongly inhibit HCV IRES-driven translation in a rabbit reticulocyte lysate assay. This inhibition was highly specific since corresponding PNAs with only one mismatch were inactive. Short phosphorothioate oligonucleotides of same sequence were unable to inhibit HCV translation. PNA molecule was shown to have anti-HCV activity in Huh-7.5 cells when electroporated with a full-length HCV genome construct. Using oligonucleotide as carrier, PNA was also transfected in HCV replicon-harboring cells and in JFH1 infected Huh-7.5 cells.</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>18625270</pmid><doi>10.1016/j.antiviral.2008.06.011</doi><tpages>8</tpages></addata></record> |
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| subjects | 5' Untranslated Regions Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antisense Antiviral agents Base Sequence Biological and medical sciences Cell Line DNA, Antisense - chemistry DNA, Antisense - genetics DNA, Antisense - pharmacology Down-Regulation - drug effects Hepacivirus - chemistry Hepacivirus - drug effects Hepacivirus - genetics Hepacivirus - metabolism Hepatitis C - drug therapy Hepatitis C - virology Hepatitis C virus Human viral diseases Humans Infectious diseases IRES JFH1 strain Medical sciences Molecular Sequence Data Peptide nucleic acid Peptide Nucleic Acids - chemistry Peptide Nucleic Acids - genetics Peptide Nucleic Acids - pharmacology Pharmacology. Drug treatments PNA Protein Biosynthesis - drug effects Rabbits Reticulocytes - metabolism Ribosomes - drug effects Ribosomes - genetics Ribosomes - metabolism Viral diseases Viral hepatitis |
| title | Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome entry site (IRES) dependent translation in vitro |
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