This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sabariegos, R.
Right arrow Articles by Martínez, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sabariegos, R.
Right arrow Articles by Martínez, M. A.

 Previous Article  |  Next Article 

Journal of Virology, January 2006, p. 571-577, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.571-577.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Sequence Homology Required by Human Immunodeficiency Virus Type 1 To Escape from Short Interfering RNAs

Rosario Sabariegos, Mireia Giménez-Barcons, Natalia Tàpia, Bonaventura Clotet, and Miguel Angel Martínez*

Fundació irsiCaixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, Ctra del Canyet s/n, 08916 Badalona, Spain

Received 22 July 2005/ Accepted 11 October 2005

Short interfering RNAs (siRNAs) targeting viral or cellular genes can efficiently inhibit human immunodeficiency virus type 1 (HIV-1) replication. Nevertheless, the emergence of mutations in the gene being targeted could lead to the rapid escape from the siRNA. Here, we simulate viral escape by systematically introducing single-nucleotide substitutions in all 19 HIV-1 residues targeted by an effective siRNA. We found that all mutant viruses that were tested replicated better in the presence of the siRNA than in the presence of the wild-type virus. The antiviral activity of the siRNA was completely abolished by single substitutions in 10 (positions 4 to 11, 14, and 15) out of 16 positions tested (substitution at 3 of the 19 positions explored rendered nonviable viruses). With the exception of the substitution observed at position 12, substitutions at either the 5' end or the 3' end (positions 1 to 3, 16, and 18) were better tolerated by the RNA interference machinery and only in part affected siRNA inhibition. Our results show that optimal HIV-1 gene silencing by siRNA requires a complete homology within most of the target sequence and that substitutions at only a few positions at the 5' and 3' ends are partially tolerated.

* Corresponding author. Mailing address: Fundació irsiCaixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, Ctra del Canyet s/n, 08916 Badalona, Spain. Phone: 34-934656374. Fax: 34-934653968. E-mail: mmartinez{at}irsicaixa.es.

Journal of Virology, January 2006, p. 571-577, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.571-577.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sugiyama, R., Habu, Y., Ohnari, A., Miyano-Kurosaki, N., Takaku, H. (2009). RNA Interference Targeted to the Conserved Dimerization Initiation Site (DIS) of HIV-1 Restricts Virus Escape Mutation. J Biochem 146: 481-489 [Abstract] [Full Text]  
  • von Eije, K. J., Brake, O. t., Berkhout, B. (2008). Human Immunodeficiency Virus Type 1 Escape Is Restricted When Conserved Genome Sequences Are Targeted by RNA Interference. J. Virol. 82: 2895-2903 [Abstract] [Full Text]  
  • Gimenez-Barcons, M., Clotet, B., Martinez, M. A. (2007). Endoribonuclease-Prepared Short Interfering RNAs Induce Effective and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication. J. Virol. 81: 10680-10686 [Abstract] [Full Text]  
  • Kanda, T., Steele, R., Ray, R., Ray, R. B. (2007). Small Interfering RNA Targeted to Hepatitis C Virus 5' Nontranslated Region Exerts Potent Antiviral Effect. J. Virol. 81: 669-676 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»