Population genomics of intrapatient HIV-1 evolution

TL;DR

This study uses longitudinal whole-genome sequencing of HIV-1 in untreated patients to reveal universal patterns of intrapatient diversity, the role of reversions, and the impact of recombination on viral evolution.

Contribution

It provides the first detailed in vivo analysis of HIV-1 evolution over years, highlighting universal diversity patterns and the effects of recombination and reversions.

Findings

Minor diversity patterns are reproducible across patients.

Reversions towards ancestral sequences are common and depend on conservation.

Recombination limits linkage disequilibrium to about 100bp.

Abstract

Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are essential. We performed whole-genome deep sequencing of HIV-1 populations in 9 untreated patients, with 6-12 longitudinal samples per patient spanning 5-8 years of infection. We show that patterns of minor diversity are reproducible between patients and mirror global HIV-1 diversity, suggesting a universal landscape of fitness costs that control diversity. Reversions towards the ancestral HIV-1 sequence are observed throughout infection and account for almost one third of all sequence changes. Reversion rates depend strongly on conservation. Frequent recombination limits linkage disequilibrium to about 100bp in most of the genome, but strong hitch-hiking due to short range linkage limits diversity.