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[Inhibitory effect of replication and expression of HDV by antisense oligodeoxynucleotides in H1 delta 9 cell]
1Center of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing.
Objective:
To study inhibitory effect of an antisense oligodeoxynucleotide (ASODN) and its phosphorothioate (S-ASODN) on replication and expression of HDV in H1 delta 9 cell.
Methods:
In previous studies, it was proved that the ASODNs which are complementary to genomic HDV ribozyme self-cleavage site and stem I regions can inhibit availably genomic HDV ribozyme activity. In the present study, a 15-mer ASODN and S-ASODS which are complementary to this region (nucleotide 684-698) were added to medium of cultured H1 delta 9 cell. HDAg and HDV cDNA were detected by ELISA and Dot blot hybridization.
Results:
Twenty-fourth hour after 6 mumol/L ASODN and S-ASODN were added, both the secreting amount of HDAg in the supernatant and HDV RNA were inhibited. The inhibiting rates were 76.14% and 84.50% respectively. When the concentration of S-ASODN was 2, 4, 6 mumol/L, the inhibiting rate showed the feature of dosage dependence. Inhibitory effect of ASODN and S-ASODN were similar in the same dosage.
Conclusion:
The results suggest that ASODN and S-ASODN can availably inhibit replication and expression of HDV in H1 delta 9 cell.
Insights
Antisense oligodeoxynucleotides (ASODN) and phosphorothioate ASODN effectively inhibit Hepatitis Delta Virus (HDV) replication and gene expression in cell cultures. These findings suggest a potential therapeutic strategy against HDV infection.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Context:
- Hepatitis Delta Virus (HDV) is a significant cause of severe liver disease.
- HDV replication relies on specific viral RNA structures, including ribozyme self-cleavage sites.
- Antisense oligodeoxynucleotides (ASODN) offer a targeted approach to inhibit viral replication.
Purpose:
- To evaluate the inhibitory efficacy of a 15-mer ASODN and its phosphorothioate derivative (S-ASODN) on HDV replication and expression.
- To determine the dose-dependent effects of these ASODNs in a cellular model.
- To assess the impact of ASODNs targeting the HDV ribozyme self-cleavage site.
Summary:
- ASODN and S-ASODN complementary to the HDV ribozyme region (nucleotides 684-698) were applied to cultured H1 delta 9 cells.
- Significant inhibition of Hepatitis Delta Antigen (HDAg) secretion and HDV RNA was observed within 24 hours.
- Inhibitory rates reached 76.14% for HDAg and 84.50% for HDV RNA, with S-ASODN showing dose-dependent effects.
Impact:
- ASODN and S-ASODN demonstrate substantial potential for inhibiting HDV replication and gene expression.
- These findings support the development of ASODN-based therapies for HDV infection.
- The study validates the targeting of specific viral RNA structures for antiviral drug development.