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Journal of Virology, September 2003, p. 9728-9731, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9728-9731.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Susceptibility of Human Hepatitis Delta Virus RNAs to Small Interfering RNA Action

Jinhong Chang and John M. Taylor*

Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111-2497

Received 18 April 2003/ Accepted 3 June 2003

In animal cells, small interfering RNAs (siRNA), when exogenously provided, have been reported to be capable of inhibiting replication of several different viruses. In preliminary studies, siRNA species were designed and tested for their ability to act on the protein expressed in Huh7 cells transfected with DNA-directed mRNA constructs containing hepatitis delta virus (HDV) target sequences. The aim was to achieve siRNA specific for each of the three RNAs of HDV replication: (i) the 1,679-nucleotide circular RNA genome, (ii) its exact complement, the antigenome, and (iii) the less abundant polyadenylated mRNA for the small delta protein. Many of the 16 siRNA tested gave >80% inhibition in this assay. Next, these three classes of siRNA were tested for their ability to act during HDV genome replication. It was found that only siRNA targeted against HDV mRNA sequences could interfere with HDV genome replication. In contrast, siRNA targeted against genomic and antigenomic RNA sequences had no detectable effect on the accumulation of these RNAs. Reconstruction experiments with nonreplicating HDV RNA sequences support the interpretation that neither the potential for intramolecular rod-like RNA folding nor the presence of the delta protein conferred resistance to siRNA. In terms of replicating HDV RNAs, it is considered more likely that the genomic and antigenomic RNAs are resistant because their location within the nucleus makes them inaccessible to siRNA-mediated degradation.

* Corresponding author. Mailing address: Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111-2497. Phone: (215) 728-2436. Fax: (215) 728-3105. E-mail: jm_taylor{at}FCCC.edu.

Journal of Virology, September 2003, p. 9728-9731, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9728-9731.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Yuan, J., Cheung, P. K. M., Zhang, H. M., Chau, D., Yang, D. (2005). Inhibition of Coxsackievirus B3 Replication by Small Interfering RNAs Requires Perfect Sequence Match in the Central Region of the Viral Positive Strand. J. Virol. 79: 2151-2159 [Abstract] [Full Text]  
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