Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site
Small interfering RNAs (siRNAs) targeting the coding region of hepatitis A virus (HAV) were shown to specifically inhibit viral genome replication. Compared to the coding region, the HAV internal ribosomal entry site (IRES) in the 5′ non-coding region is highly sequence-conserved and folds into stab...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2005-05, Vol.330 (4), p.1217-1223 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Kanda, Tatsuo Zhang, Bo Kusov, Yuri Yokosuka, Osamu Gauss-Müller, Verena |
| description | Small interfering RNAs (siRNAs) targeting the coding region of hepatitis A virus (HAV) were shown to specifically inhibit viral genome replication. Compared to the coding region, the HAV internal ribosomal entry site (IRES) in the 5′ non-coding region is highly sequence-conserved and folds into stable secondary structures. Here, we report efficient and sustained RNA interference mediated by both RNase III-prepared siRNA (esiRNA) and vector-derived short hairpin RNAs (shRNAs) that are targeted to various domains of the HAV IRES. Using reporter constructs, and the DNA-based HAV replicon system, we found that shRNAs targeting the HAV IRES domains IIIc and V sustainably suppressed genome translation and replication whereas the IRES domains IIIa and IV were resistant to RNA interference. Our study suggests that some HAV IRES domains might be used as a universal and effective target for specific inhibition of HAV infection. |
| doi_str_mv | 10.1016/j.bbrc.2005.03.105 |
| format | Article |
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Compared to the coding region, the HAV internal ribosomal entry site (IRES) in the 5′ non-coding region is highly sequence-conserved and folds into stable secondary structures. Here, we report efficient and sustained RNA interference mediated by both RNase III-prepared siRNA (esiRNA) and vector-derived short hairpin RNAs (shRNAs) that are targeted to various domains of the HAV IRES. Using reporter constructs, and the DNA-based HAV replicon system, we found that shRNAs targeting the HAV IRES domains IIIc and V sustainably suppressed genome translation and replication whereas the IRES domains IIIa and IV were resistant to RNA interference. Our study suggests that some HAV IRES domains might be used as a universal and effective target for specific inhibition of HAV infection.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2005.03.105</identifier><identifier>PMID: 15823573</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Base Sequence ; Genetic Vectors ; Genome, Viral ; HAV ; Hepatitis A virus ; Hepatitis A virus - drug effects ; Hepatitis A virus - genetics ; Hepatitis A virus - physiology ; Huh-7 ; IRES ; Molecular Sequence Data ; Nucleic Acid Conformation ; Poliovirus ; Protein Biosynthesis - drug effects ; Replicon ; Ribonuclease III - chemistry ; Ribosomes - genetics ; RNA, Small Interfering - chemical synthesis ; RNA, Small Interfering - genetics ; RNA, Small Interfering - pharmacology ; RNA, Viral - genetics ; RNAi ; shRNA ; siRNA ; Viral Proteins - biosynthesis ; Viral Proteins - genetics ; Virus Replication - drug effects ; Virus Replication - genetics</subject><ispartof>Biochemical and biophysical research communications, 2005-05, Vol.330 (4), p.1217-1223</ispartof><rights>2005 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c366t-36deee5cecd6ff96938f286c6ec12fed1ca1938cb034d5ca7bca8b2db92846cb3</citedby><cites>FETCH-LOGICAL-c366t-36deee5cecd6ff96938f286c6ec12fed1ca1938cb034d5ca7bca8b2db92846cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X05006108$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15823573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kanda, Tatsuo</creatorcontrib><creatorcontrib>Zhang, Bo</creatorcontrib><creatorcontrib>Kusov, Yuri</creatorcontrib><creatorcontrib>Yokosuka, Osamu</creatorcontrib><creatorcontrib>Gauss-Müller, Verena</creatorcontrib><title>Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Small interfering RNAs (siRNAs) targeting the coding region of hepatitis A virus (HAV) were shown to specifically inhibit viral genome replication. Compared to the coding region, the HAV internal ribosomal entry site (IRES) in the 5′ non-coding region is highly sequence-conserved and folds into stable secondary structures. Here, we report efficient and sustained RNA interference mediated by both RNase III-prepared siRNA (esiRNA) and vector-derived short hairpin RNAs (shRNAs) that are targeted to various domains of the HAV IRES. Using reporter constructs, and the DNA-based HAV replicon system, we found that shRNAs targeting the HAV IRES domains IIIc and V sustainably suppressed genome translation and replication whereas the IRES domains IIIa and IV were resistant to RNA interference. Our study suggests that some HAV IRES domains might be used as a universal and effective target for specific inhibition of HAV infection.</description><subject>Base Sequence</subject><subject>Genetic Vectors</subject><subject>Genome, Viral</subject><subject>HAV</subject><subject>Hepatitis A virus</subject><subject>Hepatitis A virus - drug effects</subject><subject>Hepatitis A virus - genetics</subject><subject>Hepatitis A virus - physiology</subject><subject>Huh-7</subject><subject>IRES</subject><subject>Molecular Sequence Data</subject><subject>Nucleic Acid Conformation</subject><subject>Poliovirus</subject><subject>Protein Biosynthesis - drug effects</subject><subject>Replicon</subject><subject>Ribonuclease III - chemistry</subject><subject>Ribosomes - genetics</subject><subject>RNA, Small Interfering - chemical synthesis</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>RNA, Viral - genetics</subject><subject>RNAi</subject><subject>shRNA</subject><subject>siRNA</subject><subject>Viral Proteins - biosynthesis</subject><subject>Viral Proteins - genetics</subject><subject>Virus Replication - drug effects</subject><subject>Virus Replication - genetics</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1r3DAQhkVpaLbb_oEeik69easPW7ahlyUkaSE00A_oTehjvNFiS64kB_bfV2YXemtPM_POM-9hXoTeUbKjhIqPx53W0ewYIc2O8KI1L9CGkp5UjJL6JdoQQkTFevrrGr1O6UgIpbXoX6Fr2nSMNy3foNP3ZZ4jpOSCx2HATzCr7LJLeI-fXVwSPoAPE-AclU9j2RVOeYsjzKMz51mfcHLfvu4TzioeIDt_wPkJsPMZolcjjk6HFKbSgc9xpTO8QVeDGhO8vdQt-nl3--Pmc_XweP_lZv9QGS5ErriwANAYMFYMQy963g2sE0aAoWwAS42iRTOa8No2RrXaqE4zq3vW1cJovkUfzr5zDL8XSFlOLhkYR-UhLEmKtuWM8fq_IG07ztfHbRE7gyaGlCIMco5uUvEkKZFrMvIo12TkmowkvGhNOXp_cV_0BPbvySWKAnw6A1Ce8ewgymQceAPWRTBZ2uD-5f8HVlSjAQ</recordid><startdate>20050520</startdate><enddate>20050520</enddate><creator>Kanda, Tatsuo</creator><creator>Zhang, Bo</creator><creator>Kusov, Yuri</creator><creator>Yokosuka, Osamu</creator><creator>Gauss-Müller, Verena</creator><general>Elsevier Inc</general><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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20050520</creationdate><title>Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site</title><author>Kanda, Tatsuo ; Zhang, Bo ; Kusov, Yuri ; Yokosuka, Osamu ; Gauss-Müller, Verena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-36deee5cecd6ff96938f286c6ec12fed1ca1938cb034d5ca7bca8b2db92846cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Base Sequence</topic><topic>Genetic Vectors</topic><topic>Genome, Viral</topic><topic>HAV</topic><topic>Hepatitis A virus</topic><topic>Hepatitis A virus - drug effects</topic><topic>Hepatitis A virus - genetics</topic><topic>Hepatitis A virus - physiology</topic><topic>Huh-7</topic><topic>IRES</topic><topic>Molecular Sequence Data</topic><topic>Nucleic Acid Conformation</topic><topic>Poliovirus</topic><topic>Protein Biosynthesis - drug effects</topic><topic>Replicon</topic><topic>Ribonuclease III - chemistry</topic><topic>Ribosomes - genetics</topic><topic>RNA, Small Interfering - chemical synthesis</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>RNA, Viral - genetics</topic><topic>RNAi</topic><topic>shRNA</topic><topic>siRNA</topic><topic>Viral Proteins - biosynthesis</topic><topic>Viral Proteins - genetics</topic><topic>Virus Replication - drug effects</topic><topic>Virus Replication - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kanda, Tatsuo</creatorcontrib><creatorcontrib>Zhang, Bo</creatorcontrib><creatorcontrib>Kusov, Yuri</creatorcontrib><creatorcontrib>Yokosuka, Osamu</creatorcontrib><creatorcontrib>Gauss-Müller, Verena</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kanda, Tatsuo</au><au>Zhang, Bo</au><au>Kusov, Yuri</au><au>Yokosuka, Osamu</au><au>Gauss-Müller, Verena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2005-05-20</date><risdate>2005</risdate><volume>330</volume><issue>4</issue><spage>1217</spage><epage>1223</epage><pages>1217-1223</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Small interfering RNAs (siRNAs) targeting the coding region of hepatitis A virus (HAV) were shown to specifically inhibit viral genome replication. Compared to the coding region, the HAV internal ribosomal entry site (IRES) in the 5′ non-coding region is highly sequence-conserved and folds into stable secondary structures. Here, we report efficient and sustained RNA interference mediated by both RNase III-prepared siRNA (esiRNA) and vector-derived short hairpin RNAs (shRNAs) that are targeted to various domains of the HAV IRES. Using reporter constructs, and the DNA-based HAV replicon system, we found that shRNAs targeting the HAV IRES domains IIIc and V sustainably suppressed genome translation and replication whereas the IRES domains IIIa and IV were resistant to RNA interference. Our study suggests that some HAV IRES domains might be used as a universal and effective target for specific inhibition of HAV infection.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15823573</pmid><doi>10.1016/j.bbrc.2005.03.105</doi><tpages>7</tpages></addata></record> |
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| subjects | Base Sequence Genetic Vectors Genome, Viral HAV Hepatitis A virus Hepatitis A virus - drug effects Hepatitis A virus - genetics Hepatitis A virus - physiology Huh-7 IRES Molecular Sequence Data Nucleic Acid Conformation Poliovirus Protein Biosynthesis - drug effects Replicon Ribonuclease III - chemistry Ribosomes - genetics RNA, Small Interfering - chemical synthesis RNA, Small Interfering - genetics RNA, Small Interfering - pharmacology RNA, Viral - genetics RNAi shRNA siRNA Viral Proteins - biosynthesis Viral Proteins - genetics Virus Replication - drug effects Virus Replication - genetics |
| title | Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site |
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