Abstract
We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.
Highlights
It is known that RNA interference (RNAi)-resistant viral mutants emerge rapidly when targeting viral sequences due to their high mutation rate [5,6,7]
We performed a detailed analysis on the HIV-1 genome to identify highly conserved targets by using 495 near full-length genome sequences of HIV-1 group M
Since many of the HIV-1 sequence entries lack 5' untranslated region (5' UTR), the 3' LTR sequence was used to compensate for the lack of 5' LTR sequences in order to avoid underestimating conservation in such regions
Summary
For RNA viruses such as HIV-1, designing functional siRNAs that target viral sequences is problematic because of their extraordinarily high genetic diversity. We performed a detailed analysis on the HIV-1 genome to identify highly conserved targets by using 495 near full-length genome sequences of HIV-1 group M (listed in Additional file 1). (page number not for citation purposes) http://www.retrovirology.com/content/4/1/80 black), conservation was calculated by considering only the HIV-1 sequences that contain the corresponding regions.
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