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Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site. | LitMetric

Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site.

Biochem Biophys Res Commun

Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.

Published: May 2005

AI Article Synopsis

  • Small interfering RNAs (siRNAs) targeting hepatitis A virus (HAV) were shown to inhibit viral genome replication effectively.
  • The study highlighted the efficiency of both siRNAs and short hairpin RNAs (shRNAs) in targeting specific conserved regions of the HAV internal ribosomal entry site (IRES), particularly domains IIIc and V, to suppress viral activity.
  • Key findings suggest that while some IRES domains can be targeted for effective virus inhibition, others, like domains IIIa and IV, are resistant to RNA interference, indicating potential strategies for therapeutic approaches.

Article 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.

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Source
http://dx.doi.org/10.1016/j.bbrc.2005.03.105DOI Listing

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