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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
Constraints on HIV-1 diversity from protein structure
Jeongmin Woo1, David L Robertson, Simon C Lovell
1Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Journal of Virology
|October 1, 2010
Summary
Understanding human immunodeficiency virus type 1 (HIV-1) evolution is key to developing vaccines and therapies. This study reveals that HIV-1 evolution is constrained by protein structure, particularly in buried regions, limiting viral change.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- The rapid evolution of human immunodeficiency virus type 1 (HIV-1) drives immune escape, drug resistance, and vaccine development challenges.
- Identifying evolutionary constraints is crucial for understanding and controlling HIV-1.
Purpose of the Study:
- To investigate the relationship between sequence diversity, selection pressures, and protein structure in HIV-1 evolution.
- To identify regions and sites under evolutionary constraint within HIV-1 proteins.
Main Methods:
- Analysis of sequence diversity and selection pressures over time.
- Examination of evolutionary rates at individual sites within HIV-1 gag and env genes.
- Mapping constrained sites onto the three-dimensional protein structure.
Main Results:
- Sequence diversity increased over time but was localized to specific structural regions.
- Substantial evolutionary constraint was observed across gag and env, even in variable envelope proteins.
- Buried protein regions showed significantly lower evolutionary rates compared to surface regions.
- Constraint was consistent across subtypes B and C and over the analyzed time period.
Conclusions:
- HIV-1 evolution is limited by structural constraints, particularly in the protein core.
- These findings elucidate the origins of evolutionary constraint and the limits of recent HIV-1 adaptation.
- Understanding these constraints can inform the development of more effective HIV-1 vaccines and therapies.
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