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Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells

BACKGROUND: Hepatitis C (HCV) viral infection is a serious medical problem in Egypt and it has a devastating impact on the Egyptian economy. It is estimated that over 15% of Egyptians are infected by the virus and thus finding a cure for this disease is of utmost importance. Current therapies for he...

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Autores principales: El Awady, Mostafa K, El Din, Noha G Badr, El Garf, Wael T, Youssef, Samar S, Omran, Moataza H, El Abd, Jasmin, Goueli, Said A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1524817/
https://www.ncbi.nlm.nih.gov/pubmed/16803625
http://dx.doi.org/10.1186/1475-2867-6-18
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author El Awady, Mostafa K
El Din, Noha G Badr
El Garf, Wael T
Youssef, Samar S
Omran, Moataza H
El Abd, Jasmin
Goueli, Said A
author_facet El Awady, Mostafa K
El Din, Noha G Badr
El Garf, Wael T
Youssef, Samar S
Omran, Moataza H
El Abd, Jasmin
Goueli, Said A
author_sort El Awady, Mostafa K
collection PubMed
description BACKGROUND: Hepatitis C (HCV) viral infection is a serious medical problem in Egypt and it has a devastating impact on the Egyptian economy. It is estimated that over 15% of Egyptians are infected by the virus and thus finding a cure for this disease is of utmost importance. Current therapies for hepatitis C virus (HCV) genotype 4 with interferon/ribavirin have not been successful and thus the development of alternative therapy for this genotype is disparately needed. RESULTS: Although previous studies utilizing viral subgenomic or full cDNA fragments linked to reporter genes transfected into adhered cells or in a cell free system showed promise, demonstration of efficient viral replication was lacking. Thus, we utilized HepG2 cells infected with native HCV RNA genomes in a replication competent system and used antisense phosphorothioate Oligonucleotides (S-ODN) against stem loop IIId and the AUG translation start site of the viral polyprotein precursor to monitor viral replication. We were able to show complete arrest of intracellular replication of HCV-4 at 1 uM S-ODN, thus providing a proof of concept for the potential antiviral activity of S-ODN on native genomic replication of HCV genotype 4. CONCLUSION: We have successfully demonstrated that by using two S-ODNs [(S-ODN1 (nt 326–348) and S-ODN-2 (nt 264–282)], we were able to completely inhibit viral replication in culture, thus confirming earlier reports on subgenomic constructs and suggesting a potential therapeutic value in HCV type 4.
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spelling pubmed-15248172006-07-29 Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells El Awady, Mostafa K El Din, Noha G Badr El Garf, Wael T Youssef, Samar S Omran, Moataza H El Abd, Jasmin Goueli, Said A Cancer Cell Int Primary Research BACKGROUND: Hepatitis C (HCV) viral infection is a serious medical problem in Egypt and it has a devastating impact on the Egyptian economy. It is estimated that over 15% of Egyptians are infected by the virus and thus finding a cure for this disease is of utmost importance. Current therapies for hepatitis C virus (HCV) genotype 4 with interferon/ribavirin have not been successful and thus the development of alternative therapy for this genotype is disparately needed. RESULTS: Although previous studies utilizing viral subgenomic or full cDNA fragments linked to reporter genes transfected into adhered cells or in a cell free system showed promise, demonstration of efficient viral replication was lacking. Thus, we utilized HepG2 cells infected with native HCV RNA genomes in a replication competent system and used antisense phosphorothioate Oligonucleotides (S-ODN) against stem loop IIId and the AUG translation start site of the viral polyprotein precursor to monitor viral replication. We were able to show complete arrest of intracellular replication of HCV-4 at 1 uM S-ODN, thus providing a proof of concept for the potential antiviral activity of S-ODN on native genomic replication of HCV genotype 4. CONCLUSION: We have successfully demonstrated that by using two S-ODNs [(S-ODN1 (nt 326–348) and S-ODN-2 (nt 264–282)], we were able to completely inhibit viral replication in culture, thus confirming earlier reports on subgenomic constructs and suggesting a potential therapeutic value in HCV type 4. BioMed Central 2006-06-27 /pmc/articles/PMC1524817/ /pubmed/16803625 http://dx.doi.org/10.1186/1475-2867-6-18 Text en Copyright © 2006 El Awady et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Primary Research
El Awady, Mostafa K
El Din, Noha G Badr
El Garf, Wael T
Youssef, Samar S
Omran, Moataza H
El Abd, Jasmin
Goueli, Said A
Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells
title Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells
title_full Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells
title_fullStr Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells
title_full_unstemmed Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells
title_short Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells
title_sort antisense oligonucleotide inhibition of hepatitis c virus genotype 4 replication in hepg2 cells
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1524817/
https://www.ncbi.nlm.nih.gov/pubmed/16803625
http://dx.doi.org/10.1186/1475-2867-6-18
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