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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
An extended stem-loop 1 is necessary for human immunodeficiency virus type 2 replication and affects genomic RNA
Jean-Marc Lanchy1, J Stephen Lodmell
1Division of Biological Sciences, The University of Montana, Missoula, MT 59812, USA.
Journal of Virology
|January 19, 2007
Summary
A specific DNA sequence in human immunodeficiency virus type 2 (HIV-2) is essential for replication and RNA packaging. Disrupting this sequence affects viral RNA encapsidation, highlighting its regulatory role.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Lentiviral genomic RNA encapsidation is a selective process, packaging two RNA molecules per virion.
- The psi signal is crucial for selecting unspliced RNA for encapsidation in lentiviruses.
Purpose of the Study:
- To investigate the role of a 10-nucleotide palindromic sequence (pal) at the 3' end of the HIV-2 psi signal in viral replication and RNA encapsidation.
- To elucidate the structural formation and functional significance of an extended stem-loop 1 (SL1) during HIV-2 replication.
Main Methods:
- Utilizing short-term and long-term cultures of pal-mutated HIV-2 viruses in C8166 cells.
- Analyzing phenotypic reversion of mutated viruses to understand structural dynamics.
- Comparing structural similarities between HIV-2 SL1 and HIV-1 stem B.
Main Results:
- The 3' palindromic sequence (pal) within the HIV-2 psi signal is critical for viral replication and genomic RNA encapsidation.
- An extended SL1 structure, involving the pal sequence, is formed during HIV-2 replication and is necessary for viability.
- Mutant viruses lacking a stable stem B, even with disrupted pal sequence, are non-viable, indicating the importance of stem stability.
Conclusions:
- Formation of the extended SL1 structure is essential for HIV-2 replication and enhances genomic RNA encapsidation.
- The pal sequence and its interaction to form SL1 play a regulatory role in the presentation of the packaging signal during the viral life cycle.
- Structural integrity of stem B within SL1 is crucial for HIV-2 viability, despite phylogenetic conservation.
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