Host-specific driving force in human immunodeficiency virus type 1 evolution in vivo

Area of Science:

• Virology
• Evolutionary Biology
• Immunology

Background:

• Understanding human immunodeficiency virus type 1 (HIV-1) evolution in vivo is crucial for developing effective treatments and vaccines.
• Previous hypotheses suggested neutral or mutation-driven evolution, or chance events, govern HIV-1 diversification.

Purpose of the Study:

• To investigate the in vivo evolutionary mechanisms of HIV-1, specifically focusing on the V3 loop and flanking regions.
• To determine the role of positive selection versus neutral drift in HIV-1 env V3 evolution.

Main Methods:

• Sequencing of 179 HIV-1 V3 plasma samples from three linked individuals over up to 8 years.
• Systematic pairwise comparison of intrapatient sequences to analyze synonymous and nonsynonymous substitutions.
• Analysis of evolutionary rates within and between infected individuals.

Main Results:

• A significant accumulation of nonsynonymous substitutions over synonymous ones in the HIV-1 V3 loop and flanking regions.
• Demonstrated host-dependent variation in HIV-1 evolution rates, even with the same viral strain.
• Observed similar divergence rates within and between individuals, indicating transmission does not reset the evolutionary clock.

Conclusions:

• Positive selection for amino acid change is the dominant force shaping HIV-1 env V3 evolution in vivo.
• HIV-1 evolution is significantly influenced by host-specific factors.
• The genetic divergence process in the HIV epidemic is continuous and not reset by transmission events.