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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
M T Boswell1, J Nazziwa2, K Kuroki3
1Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, OX3 7FZ, Oxford, UK.
Virus Evolution
|December 19, 2022
Summary
Human Immunodeficiency Virus type 2 (HIV-2) p26 capsid evolution is linked to disease progression. Faster evolving HIV-2 p26 sequences correlate with quicker disease advancement and may represent a therapeutic target.
Area of Science:
- Virology
- Immunology
- Evolutionary Biology
Background:
- HIV-2 infection progresses to AIDS slower than HIV-1.
- HIV-2 p26 (capsid) polymorphisms and env evolution are linked to slower disease progression.
- Understanding HIV-2 evolution is crucial for identifying therapeutic targets.
Purpose of the Study:
- To analyze HIV-2 p26 sequence evolution in relation to disease progression.
- To determine if evolutionary parameters of p26 are associated with faster or slower progression to AIDS.
- To identify specific p26 amino acid sites and evolutionary rates linked to disease progression.
Main Methods:
- Analysis of 369 heterochronous HIV-2 p26 sequences from 12 participants.
- Stratification of participants into faster and slower progressor groups based on CD4% change.
- Measurement of p26 sequence diversity, site-specific selection pressures, and evolutionary rates.
Main Results:
- Faster progressors exhibited higher p26 sequence diversity and significantly higher virus evolutionary rates (synonymous and nonsynonymous).
- Virus evolutionary rates negatively correlated with CD4% decline rates.
- Distinct amino acid signatures at p26 positions 6, 12, and 119 were observed between faster and slower progressors, near the TRIM5α/p26 interface.
Conclusions:
- HIV-2 p26 evolutionary rates are associated with AIDS progression, primarily driven by synonymous substitutions.
- Limited nonsynonymous evolution suggests p26 is relatively conserved within hosts.
- HIV-2 p26 represents a potential therapeutic target due to its association with disease progression.
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