Hidden messages in the nef gene of human immunodeficiency virus type 1 suggest a novel RNA secondary structure
Related Experiment Video
Updated: Jul 19, 2026

RNA Secondary Structure Prediction Using High-throughput SHAPE
Published on: May 31, 2013
Ofer Peleg1, Edward N Trifonov, Alexander Bolshoy
1Genome Diversity Center, Institute of Evolution, Haifa University, Mt Carmel, Haifa 31905, Israel.
Abstract:
The coexistence of multiple codes in the genome of human immunodeficiency virus type 1 (HIV-1) was analyzed. We explored factors constraining the variability of the virus genome primarily in relation to conserved RNA secondary structures overlapping coding sequences, and used a simple combination of algorithms for RNA secondary structure prediction based on the nearest-neighbor thermodynamic rules and a statistical approach. In our previous study, we applied this combination to a non- redundant data set of env nucleotide sequences, confirmed the conservative secondary structure of the rev-responsive element (RRE) and found a new RNA structure in the first conserved (C1) region of the env gene. In this study, we analyzed the variability of putative RNA secondary structures inside the nef gene of HIV-1 by applying these algorithms to a non-redundant data set of 104 nef sequences retrieved from the Los Alamos HIV database, and predicted the existence of a novel functional RNA secondary structure in the beta3/beta4 regions of nef. The predicted RNA fold in the beta3/beta4 region of nef appears in two forms with different loop sizes. The loop of the first fold consists of seven nucleotides (positions 494-500), with consensus UCAAGCU appearing in 79% of sequences. The other has a five-base loop (positions 495-499) with consensus CAAGC. The difference in size between these two loops may reflect the difference between respective counterparts in the hairpin recognition. This may also have an adaptive biological significance.
Related Concept Videos
Viral Mutations
Retroviruses
Leaky Scanning
Size and Structure of Viral Genomes
Viruses with RNA Genomes
Inhibitors of Virion Maturation and Assembly

