In vitro and in vivo protection against the highly pathogenic H5N1 influenza virus by an antisense phosphorothioate oligonucleotide
Current vaccination strategies and antiviral drugs only provide limited protection against influenza virus infection. In this study, we investigated the use of a novel antisense oligonucleotide (named IV-AS), which is specific for the 5'-terminal conserved sequence found in all eight viral RNA...
Saved in:
| Published in: | Antiviral therapy Vol. 13; no. 1; p. 109 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
2008
|
| Subjects: | |
| ISSN: | 1359-6535 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Current vaccination strategies and antiviral drugs only provide limited protection against influenza virus infection. In this study, we investigated the use of a novel antisense oligonucleotide (named IV-AS), which is specific for the 5'-terminal conserved sequence found in all eight viral RNA segments of influenza A virus.
The activity of IV-AS was monitored both in vitro, in Madin-Darby canine kidney (MDCK) cells, and in vivo using a mouse model. IV-AS was given intranasally to H5N1-infected mice once daily for 6 days starting 6 h after infection. A three-base mismatch of IV-AS was used as a control.
IV-AS inhibited influenza virus A induced cytopathic effects in MDCK cells with the 50% effective concentration (EC50) ranging from 2.2 to 4.4 microM. IV-AS was effective against H5N1 virus in preventing death, lessening weight reduction, inhibiting lung consolidation and reducing lung virus titres. Dosages of 40 and 60 mg/kg/day provided 40% and 60% survival rates and prolonged mean survival days in comparison with the infected control group (P<0.05). The lung index in mice treated with IV-AS, at a dose of 20, 40 or 60 mg/kg/day, had been inhibited on day 4 or 6 (P<0.05 or P<0.01); virus titres in lung had declined to 2.42, 1.51 and 1.54 log10 TCID50/g of lung, respectively, whereas the yields in the infected control mice were 6.00 log10 TCID50/g of lung.
Our results suggest that the 5'-terminal conserved region of influenza A virus RNA segments can be targeted using antisense technology; therefore, IV-AS is a potential drug for prophylaxis and control of influenza virus infections. |
|---|---|
| AbstractList | Current vaccination strategies and antiviral drugs only provide limited protection against influenza virus infection. In this study, we investigated the use of a novel antisense oligonucleotide (named IV-AS), which is specific for the 5'-terminal conserved sequence found in all eight viral RNA segments of influenza A virus.
The activity of IV-AS was monitored both in vitro, in Madin-Darby canine kidney (MDCK) cells, and in vivo using a mouse model. IV-AS was given intranasally to H5N1-infected mice once daily for 6 days starting 6 h after infection. A three-base mismatch of IV-AS was used as a control.
IV-AS inhibited influenza virus A induced cytopathic effects in MDCK cells with the 50% effective concentration (EC50) ranging from 2.2 to 4.4 microM. IV-AS was effective against H5N1 virus in preventing death, lessening weight reduction, inhibiting lung consolidation and reducing lung virus titres. Dosages of 40 and 60 mg/kg/day provided 40% and 60% survival rates and prolonged mean survival days in comparison with the infected control group (P<0.05). The lung index in mice treated with IV-AS, at a dose of 20, 40 or 60 mg/kg/day, had been inhibited on day 4 or 6 (P<0.05 or P<0.01); virus titres in lung had declined to 2.42, 1.51 and 1.54 log10 TCID50/g of lung, respectively, whereas the yields in the infected control mice were 6.00 log10 TCID50/g of lung.
Our results suggest that the 5'-terminal conserved region of influenza A virus RNA segments can be targeted using antisense technology; therefore, IV-AS is a potential drug for prophylaxis and control of influenza virus infections. Current vaccination strategies and antiviral drugs only provide limited protection against influenza virus infection. In this study, we investigated the use of a novel antisense oligonucleotide (named IV-AS), which is specific for the 5'-terminal conserved sequence found in all eight viral RNA segments of influenza A virus.BACKGROUNDCurrent vaccination strategies and antiviral drugs only provide limited protection against influenza virus infection. In this study, we investigated the use of a novel antisense oligonucleotide (named IV-AS), which is specific for the 5'-terminal conserved sequence found in all eight viral RNA segments of influenza A virus.The activity of IV-AS was monitored both in vitro, in Madin-Darby canine kidney (MDCK) cells, and in vivo using a mouse model. IV-AS was given intranasally to H5N1-infected mice once daily for 6 days starting 6 h after infection. A three-base mismatch of IV-AS was used as a control.METHODSThe activity of IV-AS was monitored both in vitro, in Madin-Darby canine kidney (MDCK) cells, and in vivo using a mouse model. IV-AS was given intranasally to H5N1-infected mice once daily for 6 days starting 6 h after infection. A three-base mismatch of IV-AS was used as a control.IV-AS inhibited influenza virus A induced cytopathic effects in MDCK cells with the 50% effective concentration (EC50) ranging from 2.2 to 4.4 microM. IV-AS was effective against H5N1 virus in preventing death, lessening weight reduction, inhibiting lung consolidation and reducing lung virus titres. Dosages of 40 and 60 mg/kg/day provided 40% and 60% survival rates and prolonged mean survival days in comparison with the infected control group (P<0.05). The lung index in mice treated with IV-AS, at a dose of 20, 40 or 60 mg/kg/day, had been inhibited on day 4 or 6 (P<0.05 or P<0.01); virus titres in lung had declined to 2.42, 1.51 and 1.54 log10 TCID50/g of lung, respectively, whereas the yields in the infected control mice were 6.00 log10 TCID50/g of lung.RESULTSIV-AS inhibited influenza virus A induced cytopathic effects in MDCK cells with the 50% effective concentration (EC50) ranging from 2.2 to 4.4 microM. IV-AS was effective against H5N1 virus in preventing death, lessening weight reduction, inhibiting lung consolidation and reducing lung virus titres. Dosages of 40 and 60 mg/kg/day provided 40% and 60% survival rates and prolonged mean survival days in comparison with the infected control group (P<0.05). The lung index in mice treated with IV-AS, at a dose of 20, 40 or 60 mg/kg/day, had been inhibited on day 4 or 6 (P<0.05 or P<0.01); virus titres in lung had declined to 2.42, 1.51 and 1.54 log10 TCID50/g of lung, respectively, whereas the yields in the infected control mice were 6.00 log10 TCID50/g of lung.Our results suggest that the 5'-terminal conserved region of influenza A virus RNA segments can be targeted using antisense technology; therefore, IV-AS is a potential drug for prophylaxis and control of influenza virus infections.CONCLUSIONSOur results suggest that the 5'-terminal conserved region of influenza A virus RNA segments can be targeted using antisense technology; therefore, IV-AS is a potential drug for prophylaxis and control of influenza virus infections. |
| Author | Zhou, Zhe Lin, Ru-Xian Wang, Sheng-Qi Yang, Jing Duan, Ming Xia, Xian-Zhu |
| Author_xml | – sequence: 1 givenname: Ming surname: Duan fullname: Duan, Ming organization: Beijing Institute of Radiation Medicine, Beijing 100850, PR China – sequence: 2 givenname: Zhe surname: Zhou fullname: Zhou, Zhe – sequence: 3 givenname: Ru-Xian surname: Lin fullname: Lin, Ru-Xian – sequence: 4 givenname: Jing surname: Yang fullname: Yang, Jing – sequence: 5 givenname: Xian-Zhu surname: Xia fullname: Xia, Xian-Zhu – sequence: 6 givenname: Sheng-Qi surname: Wang fullname: Wang, Sheng-Qi |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18389905$$D View this record in MEDLINE/PubMed |
| BookMark | eNo1kMtOwzAQRb0oog_4ARbIK3YBP5N4iSqglSrYwDpykklilNohdiqVLT-OK4o0o9Fc3XukmSWaWWcBoRtK7inNsgfKpUollyQnlBNCKZuhxUlMTuocLb3_JITlipBLNKc5z5UicoF-thYfTBgd1rbG5rQcHB5GF6AKxlmsW22sDzh0gDvTdv0RDzp0rgVrKryRrzSmmn4C-61jeJw8Lo8RFisYD9YDHjrnY0dmZ5wOgF1vWmenqgcXTA1X6KLRvYfr81yhj-en9_Um2b29bNePu6QSGQsJq2WtRMabRqu0yQgwTpq0TnkuCBekEiC5ogyEVGUpFWdaC17lQjcs5yUotkJ3f9x43tcEPhR74yvoe23BTb7ISKQrSaPx9mycyj3UxTCavR6Pxf_b2C-PB3G5 |
| CitedBy_id | crossref_primary_10_1016_j_antiviral_2011_06_013 crossref_primary_10_1038_s41598_019_40443_7 crossref_primary_10_3390_ijms24021232 crossref_primary_10_1016_j_jbiotec_2015_06_391 crossref_primary_10_3390_v6020573 crossref_primary_10_3390_jcm8010006 crossref_primary_10_1089_nat_2011_0310 crossref_primary_10_1016_j_intimp_2011_08_019 crossref_primary_10_1016_j_vaccine_2010_12_088 crossref_primary_10_1371_journal_pcbi_1004663 crossref_primary_10_4155_fmc_15_112 crossref_primary_10_1089_nat_2016_0619 crossref_primary_10_1007_s00705_009_0380_2 crossref_primary_10_1134_S1068162019060268 crossref_primary_10_1007_s00705_014_2054_y crossref_primary_10_3390_pathogens9110925 crossref_primary_10_1016_j_antiviral_2013_10_005 crossref_primary_10_1093_cid_cir107 crossref_primary_10_1016_j_jchromb_2008_11_036 crossref_primary_10_1007_s00216_012_5935_5 crossref_primary_10_3390_v20801530 crossref_primary_10_1016_j_tetlet_2013_10_129 crossref_primary_10_1016_j_molcel_2020_07_027 crossref_primary_10_3762_bjnano_7_108 crossref_primary_10_1016_j_bbrc_2009_09_039 crossref_primary_10_1016_j_ejpb_2021_03_006 crossref_primary_10_1016_j_omtn_2017_10_001 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1177/135965350801300112 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Pharmacy, Therapeutics, & Pharmacology |
| ExternalDocumentID | 18389905 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | --- 0R~ 23M 53G 5GY AABMB AADUE AARIX AASGM ABJIS ABQXT ABRHV ACARO ACHEB ACIRW ACOFE ACVXM ADBBV ADOGD AENEX AEXNY AFCOW AFRWT AGNHF AJINM ALMA_UNASSIGNED_HOLDINGS BAWUL BKSCU CGR CUY CVF DC- DIK EBS ECM EIF EJD EMOBN F5P GROUPED_DOAJ H13 J8X NPM OK1 P2P Q1R SAUOL SCDPB SCNPE SFC TRC W2D ZONMY ZSSAH 7X8 |
| ID | FETCH-LOGICAL-c472t-2d5d9473ffa96f70e230f6d63840340c4e53912e459bb5932aa43c84af283be92 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 29 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000254003200012&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1359-6535 |
| IngestDate | Fri Jul 11 07:15:52 EDT 2025 Mon Jul 21 05:43:08 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 1 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c472t-2d5d9473ffa96f70e230f6d63840340c4e53912e459bb5932aa43c84af283be92 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://journals.sagepub.com/doi/pdf/10.1177/135965350801300112 |
| PMID | 18389905 |
| PQID | 70473951 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_70473951 pubmed_primary_18389905 |
| PublicationCentury | 2000 |
| PublicationDate | 2008-00-00 20080101 |
| PublicationDateYYYYMMDD | 2008-01-01 |
| PublicationDate_xml | – year: 2008 text: 2008-00-00 |
| PublicationDecade | 2000 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England |
| PublicationTitle | Antiviral therapy |
| PublicationTitleAlternate | Antivir Ther |
| PublicationYear | 2008 |
| SSID | ssj0028900 |
| Score | 1.9668345 |
| Snippet | Current vaccination strategies and antiviral drugs only provide limited protection against influenza virus infection. In this study, we investigated the use of... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 109 |
| SubjectTerms | Animals Cell Line Cytopathogenic Effect, Viral Dogs Dose-Response Relationship, Drug Influenza A Virus, H5N1 Subtype - immunology Lung - pathology Lung - virology Mice Mice, Inbred BALB C Oligonucleotides, Antisense - adverse effects Oligonucleotides, Antisense - immunology Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - virology Phosphorothioate Oligonucleotides - adverse effects Phosphorothioate Oligonucleotides - immunology Specific Pathogen-Free Organisms Time Factors |
| Title | In vitro and in vivo protection against the highly pathogenic H5N1 influenza virus by an antisense phosphorothioate oligonucleotide |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/18389905 https://www.proquest.com/docview/70473951 |
| Volume | 13 |
| WOSCitedRecordID | wos000254003200012&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8NAEF7UevDi-1Gfc5CeGsxjt2lAEBFLBS09VOitbJLdNlCytWkL9eofdyZp7Ek8CEkgC7sku7Oz3-zszMfYrY9rmg5tadmxG1qcppR0ncjiTQfRNlpEIs5T5r_6nU6z3w-6G-y-jIWhY5WlTswVdWwi2iO_821OPiXnYfJhEWcU-VZXBBqbrOIhkCGZ9vs_PgTyoBUxwoIOeHiiDJmhYHMsoyKES-TOcYiP8jeAmS80rb3_feI-210BTHgsJOKAbaj0kNW6RYbqZR1664CrrA416K5zVy-P2NdLCotkNjUg0xgSelkYWCVzwCEEOZQJIkpA3AiU6ni8BCI1NiiHSQRt0XGwVs578imx8nSeQbjExvAi2uc0UzAZmQxvbHOUGIS6YMbJ0KSUWNnMklgds_fWc--pba14GqyI--7McmMRB_jrWsugoX1boVmjGzHObG573I64El7guIqLIAwFAkYpuRc1udSIbUIVuCdsKzWpOmPgeg3pRU5D8xBtdl8FCKddHWhf2lqiXFXZTdn1A5wH5NyQqTLzbFB2fpWdFqM3mBTpOgaotNCotMX5n3Uv2E5xHIR2WC5ZRaMGUFdsO1pgD02vc_HCZ6f79g2NZ9tp |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=In+vitro+and+in+vivo+protection+against+the+highly+pathogenic+H5N1+influenza+virus+by+an+antisense+phosphorothioate+oligonucleotide&rft.jtitle=Antiviral+therapy&rft.au=Duan%2C+Ming&rft.au=Zhou%2C+Zhe&rft.au=Lin%2C+Ru-Xian&rft.au=Yang%2C+Jing&rft.date=2008-01-01&rft.issn=1359-6535&rft.volume=13&rft.issue=1&rft.spage=109&rft_id=info:doi/10.1177%2F135965350801300112&rft_id=info%3Apmid%2F18389905&rft_id=info%3Apmid%2F18389905&rft.externalDocID=18389905 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1359-6535&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1359-6535&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1359-6535&client=summon |