الفهرس 
Hepatitis C virus
2.3.1Distribution of HCV genotypes WorldwideOnly 14 pages are availabe for public view
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Abstract
Introduction: Although interferon and ribavirin combined therapy is the only approved HCV therapy, this therapy is costly, prolonged, and is associated with significant adverse effects. Furthermore; its outcome is unfortunately poor with genotype 4. Development of alternative therapy for this genotype is of a paramount importance. Inhibitions of HCV gene expression in vitro by the use of antisense phosphorothioate oligodeoxynucleotides (S-ODN) against internal ribosome entry site (IRES) elements were associated with favorable results. Methods: To assess S-ODN activity, IRES domain III derived from nine Egyptian patients infected with genotype 4a were amplified, cloned and sequenced. In addition, IRES domain IV sequences that belongs to another group of patients infected with genotype 4a that were previously performed in our laboratory were obtained from GenBank. Alignment of both domains revealed that domain IV is highly conserved over loop III d which showed less sequence conservation. Such conservation suggests higher efficiency of S-ODN1 (directed against domain IV) than S-ODN2 (directed against loop III d). Effect of mismatched oligonucleotides on intracellular HCV RNA levels was also studied by using S-ODN1 altered sequence (S-ODN1*) after random introduction of a single nucleotide substitution which showed no significant effect on S-ODN1 inhibitory effect on viral replication. The efficiency of S-ODN1 to inhibit viral replication in two different cell types was then investigated using HepG2 cells and PBMCs. Results: The current study have shown that SODN1 was efficiently able to inhibit viral replication in infected HepG2 cells while; in contrast, it failed to inhibit viral replication in PBMCs. Conclusion: The antisense oligonucleotides displayed differential inhibitory effects in different types of HCV permissible cells suggesting that S-ODN1 may inhibit HCV replication via cell specific mechanisms (pathways).
Key words:
HCV, S-ODN, IRES, alignment, HepG2, PBMCs, viral replication
Supervisors
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Prof.Dr. Mohamed Shoukry
Chairman of Chemistry Department
Faculty of Science- Cairo University