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Structural Fluidity of the Human Immunodeficiency Virus Rev Response Element
Chringma Sherpa1, Stuart F J Le Grice1
1Basic Research Laboratory, National Cancer Institute, Frederick, MD 21701, USA.
Viruses
|January 17, 2020
Summary
The human immunodeficiency virus (HIV) Rev response element (RRE) exhibits structural flexibility, with 4 or 5 stem-loops (SLs). This flexibility influences viral replication and offers a therapeutic target.
Area of Science:
- Molecular Biology
- Virology
- Structural Biology
Background:
- Nucleocytoplasmic transport of human immunodeficiency virus (HIV) RNA relies on the Rev response element (RRE).
- The RRE's structure, specifically its stem-loop (SL) count (4 or 5 SLs), has been debated for decades.
- Understanding RRE topology is crucial for comprehending HIV replication and developing therapies.
Purpose of the Study:
- To review evidence on the structural flexibility of HIV-1 and HIV-2 RREs.
- To explore the biological significance of RRE topology, including 4 SL and 5 SL conformers.
- To discuss the therapeutic potential of RRE conformational flexibility.
Main Methods:
- Review of existing literature and structural studies on RRE.
- Analysis of in vitro mutagenesis data on RRE conformers.
- Examination of clinical data on RRE evolution in patient isolates.
Main Results:
- HIV-1 and HIV-2 RREs demonstrate significant conformational flexibility.
- The 5 SL RRE conformer shows a growth advantage in cell culture studies.
- RRE structural rearrangements are linked to HIV-1 resistance to trans-dominant Rev therapy.
- RRE topology evolves in patient isolates.
Conclusions:
- RRE conformational flexibility is a key feature of HIV biology.
- The 5 SL RRE conformer may confer a selective advantage.
- RRE flexibility presents a promising target for novel antiviral therapies.
- High-throughput screening can exploit RRE conformational flexibility for drug discovery.
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