The HIV-2 Rev-response element: determining secondary structure and defining folding intermediates

Area of Science:

• Molecular Biology
• Virology
• Structural Biology

Background:

• The interaction between viral protein Rev and Rev response elements (RREs) is crucial for HIV RNA transport.
• Understanding these nucleoprotein complexes can lead to new antiviral drug development targeting RNA regulatory signals.

Purpose of the Study:

• To identify the secondary structures of the HIV-2 RRE and its folding precursors.
• To investigate the conformational transitions of the HIV-2 RRE.

Main Methods:

• Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemical probing.
• A novel mathematical approach for RNA secondary structure determination.
• Complementary chemical probing techniques.

Main Results:

• The secondary structures of the HIV-2 RRE and two folding precursors were identified.
• Evidence for two conformational transitions in the HIV-2 RRE before reaching its final structure was found.
• 3D models of the HIV-2 RRE and its folding intermediates were generated.

Conclusions:

• The HIV-2 RRE undergoes significant conformational transitions.
• The Rev-binding stem-loops (IIB and I) are coaxially located in the final HIV-2 RRE structure.
• These findings support previous models of HIV-1 Rev-RRE binding and offer insights for antiviral drug design.