Comparative study of adaptive molecular evolution in different human immunodeficiency virus groups and subtypes

Area of Science:

• Virology
• Evolutionary Biology
• Immunology

Background:

• Human immunodeficiency virus type 1 (HIV-1) exhibits rapid evolution driven by host immune responses.
• Understanding molecular adaptation and positive selection is crucial for developing effective antiviral strategies.

Purpose of the Study:

• To quantify molecular adaptation in HIV-1 group M subtypes, group O, and HIV-2.
• To investigate the location and strength of positive selection within the HIV-1 env gene across different subtypes.
• To correlate positively selected sites with host immune epitopes and glycosylation sites.

Main Methods:

• Utilized a codon-based maximum-likelihood method to detect positive selection in viral genes (gag, pol, env).
• Compared HIV-1 sequence alignments from various subtypes (M, O) and HIV-2.
• Analyzed the positional correlation of selected sites with antibody, T-helper, and cytotoxic T lymphocyte epitopes, and N/O-glycosylation sites.

Main Results:

• Identified varying numbers of positively selected sites across different HIV-1 alignments (25-40 sites).
• Observed a significant tendency for positively selected sites to occupy similar positions across diverse HIV-1 alignments (10-16 shared sites in group M, 6-8 in group O vs. M).
• Found that positively selected sites are frequently located outside T-helper epitopes and strongly associated with N-glycosylation sites.

Conclusions:

• HIV-1 variants are subjected to similar selective forces, driving adaptive evolution.
• Conserved positively selected sites suggest common mechanisms for viral persistence.
• The association of selected sites with N-glycosylation sites and their location outside T-helper epitopes may inform future therapeutic targets.