Host-specific modulation of the selective constraints driving human immunodeficiency virus type 1 env gene evolution

Area of Science:

• Virology
• Evolutionary Biology
• Immunology

Background:

• Human immunodeficiency virus type 1 (HIV-1) exhibits significant intra-host evolution.
• Understanding HIV-1 evolutionary dynamics is crucial for predicting disease progression and developing effective treatments.

Purpose of the Study:

• To investigate the differences in HIV-1 evolution between typical progressors (TPs) and slow progressors (SPs) within individual hosts.
• To analyze the evolutionary patterns of the C2-V5 env regions from both cell-free RNA and proviral DNA.

Main Methods:

• Analysis of 506 molecular clones (253 RNA, 253 DNA) from the C2-V5 env regions of HIV-1.
• Sequential sampling over 3 years from six untreated subjects (3 TPs, 3 SPs).
• Comparative evolutionary analysis of nucleotide similarity, divergence, host-selective pressure, and substitution rates (Ka/Ks).

Main Results:

• Slow progressors (SPs) showed lower nucleotide similarity and higher intra- and intersample divergence in both DNA and RNA clones compared to typical progressors (TPs).
• Higher host-selective pressure was generally observed in SPs.
• Evolutionary rates differed, with TPs showing increases in both synonymous (Ks) and nonsynonymous (Ka) substitutions, while SPs primarily showed increases in Ka.

Conclusions:

• Distinct evolutionary pathways exist for HIV-1 in TPs and SPs, influenced by host-specific selective pressures.
• The analysis of env hypervariable regions and Ka/Ks ratios provides insights into host-virus interactions and modulation of selective constraints.