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Cited by 398

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome

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Westerhout, E. M.·2005·Nucleic Acids Research

Abstract

HIV-1 replication can be efficiently inhibited by intracellular expression of an siRNA targeting the viral RNA. However, HIV-1 escape variants emerged after prolonged culturing. These RNAi-resistant viruses contain nucleotide substitutions or deletions in or near the targeted sequence. We observed an inverse correlation between the level of resistance and the stability of the siRNA/target-RNA duplex. However, two escape variants showed a higher level of resistance than expected based on the duplex stability. We demonstrate that these mutations induce alternative folding of the RNA such that the target sequence is occluded from binding to the siRNA, resulting in reduced RNAi efficiency. HIV-1 can thus escape from RNAi-mediated inhibition not only through nucleotide substitutions or deletions in the siRNA target sequence, but also through mutations that alter the local RNA secondary structure. The results highlight the enormous genetic flexibility of HIV-1 and provide detailed molecular insight into the sequence specificity of RNAi and the impact of target RNA secondary structure.

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Metadata

Authors
Westerhout, E. M.
Venue
Nucleic Acids Research
Published
2005-01-19
Volume
33
Issue
2
Pages
796-804
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2069608350
Cited by
398
References
41
FWCI
17.63
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome. https://app.cochat.ai/papers/10.1093/nar/gki220
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Westerhout, E. M. (2005). HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome. Nucleic Acids Research. https://doi.org/10.1093/nar/gki220

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