HIV-1 resistance to the anti-HIV activity of a shRNA targeting a dual-coding region

Jordi Senserrich, Eduardo Pauls, Mercedes Armand-Ugón, Imma Clotet-Codina, Gemma Moncunill, Bonaventura Clotet, Jose A. Esté

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)


We generated a lymphoid cell line (Sup-T1-Rev/Env) that stably expresses a 19-bp short hairpin RNA (shRNA) targeting a conserved region of HIV-1 encoding for the Envelope and Rev proteins, which potently inhibited viral replication. However, continuous passage of HIV-1 in Sup-T1-Rev/Env generated virus mutants able to overcome the RNAi restriction. Sequence analysis of the emerging viruses showed that mutations were located at positions 5 and 17 of the target sequence. Both mutations are silent in the Env frame, but the mutation 5 generated an amino acid change (V47M) in the Rev reading frame. We have analyzed the impact of these two mutations on the RNAi mechanism, showing a more crucial role of the mutation 17 in the resistance to RNAi. We show that even targeting a conserved region of the HIV-1 genome involved in the biosynthesis of two essential genes, env and rev, the virus could evolve to escape by single point mutations in the target sequence, without a significant fitness cost. © 2007 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)421-429
Issue number2
Publication statusPublished - 15 Mar 2008


  • HIV
  • Resistance
  • RNA interference
  • Viral evolution


Dive into the research topics of 'HIV-1 resistance to the anti-HIV activity of a shRNA targeting a dual-coding region'. Together they form a unique fingerprint.

Cite this