Conflicting selection pressures on T-cell epitopes in HIV-1 subtype B

Area of Science:

• Molecular Evolution
• Virology
• Immunology

Background:

• Understanding the evolutionary dynamics of human immunodeficiency virus type 1 (HIV-1) is crucial for developing effective treatments and vaccines.
• Population-level genetic variation within HIV-1 subtype B provides insights into selective pressures shaping its genome.
• Epitopes recognized by host immune cells (CD4 and CTL) are key targets for immune responses and potential sites of viral adaptation.

Purpose of the Study:

• To analyze population-level polymorphism in eight coding genes of HIV-1 subtype B.
• To investigate the role of purifying selection on nonsynonymous variants, particularly within CD4 and CTL epitopes.
• To explore the evolutionary conflict between immune escape and functional constraint in HIV-1 epitopes.

Main Methods:

• Analysis of genetic polymorphism across eight coding genes of HIV-1 subtype B.
• Identification and characterization of nonsynonymous variants, including singletons.
• Comparison of gene diversity at polymorphic nonsynonymous sites located within and outside CD4 and CTL epitopes.

Main Results:

• Evidence of both past purifying selection and ongoing selection against slightly deleterious nonsynonymous variants in HIV-1 subtype B.
• An excess of nonsynonymous singletons observed in both CD4 and CTL epitopes.
• Lower median gene diversity at polymorphic nonsynonymous sites within CD4 epitopes compared to other sites.

Conclusions:

• The findings support an evolutionary conflict between immune escape and functional constraint on T-cell epitopes.
• Amino acid sequences within CD4 epitopes are under particularly strong functional constraint.
• Purifying selection plays a significant role in shaping the evolution of HIV-1, even on slightly deleterious variants.