The intra-host evolutionary and population dynamics of human immunodeficiency virus type 1: a phylogenetic perspective

Abstract

The intra-host evolutionary and population dynamics of the human immunodeficiency virus type 1 (HIV-1), the cause of the acquired immunodeficiency syndrome, have been the focus of one of the most extensive study efforts in the field of molecular evolution over the past three decades. As HIV-1 is among the fastest mutating organisms known, viral sequence data sampled over time from infected patients can provide, through phylogenetic analysis, significant insights about the tempo and mode of evolutionary processes shaped by complex interaction with the host milieu. Five main aspects are discussed: the patterns of HIV-1 intra-host diversity and divergence over time in relation to different phases of disease progression; the impact of selection on the temporal structure of HIV-1 intra-host genealogies inferred from longitudinally sampled viral sequences; HIV-1 intra-host sub-population structure; the potential relationship between viral evolutionary rate and disease progression and the central evolutionary role played by recombination occurring in super-infected cells.

Keywords: HIV-1; intrahost evolution; phylogenetic analysis; population dynamics.

Figure 1.

Maximum likelihood genealogies of HIV-1 intra-host sequences sampled over time from two different subjects. The trees were obtained with the HKY+G model. Branch lengths are scaled in nucleotide substitutions per site according to the bar at the bottom of each tree. The number after the @ sign in the sequence label indicates the sampling time in days post infection. Sequence names from different time points are displayed in different colors for clarity. The colored circles highlights the internal nodes representing the most recent common ancestor of the viral population sampled at a given time point. The root was inferred by choosing the rooted topology that resulted in the best linear regression between branch lengths and sampling times. The tree for subject S4 (left) includes a subset of env gp120 V1V3 sequences described in Salemi et al. (2007) from a pediatric patient infected through mother to child transmission. The tree for subject P5 (right) includes a subset of gag p24 sequences described in Norstrom et al. (2012) from a patient carrying the HLA-B*5701 allele with low risk of disease progression. Sequences sampled at a later time point clustering with sequences sampled earlier are indicated by arrows and may reveal archival genomes from viral reservoirs. The alignments used in the analysis are available from the author upon request.

Figure 2.

Maximum likelihood genealogy of HIV-1 gp120 V3C4 sequences amplified from necropsy tissues of a patient with widespread atherosclerosis. The tree includes a subset of the sequences obtained from subject AZ described in Lamers et al. (2011), and was inferred using the HKY+G model. Branch lengths are scaled in nucleotide substitutions per site according to the bar at the bottom and colored to highlight the tissue of origin according to the legend in the figure. The tissue of origin of the internal branches was inferred by maximum parsimonious reconstruction of ancestral states. Numbers along the branches represent percent bootstrap values (1000 replicates). The alignment used in the analysis is available from the author upon request.

Figure 3.

Putative recombination analysis of HIV-1 intra-host sequences sampled from different tissues as indicated by the color legend in the figure. A query sequence is compared to a set of reference sequences by a sliding window analysis, which calculates the bootstrap support for the clustering of the query sequence with a specific reference sequence along the genome. In this cartoon example, a query sequence from plasma clusters with high bootstrap support with a reference sequence from peripheral blood mononuclear cells (PBMCs) in the 5’ end of the genome, while with a sequence from thymus in the 3’ end. The two trees are schematically illustrated within the frame and the network shows how they could be represented by a cyclic graph where the recombinant sequence is simultaneously connected to the putative parental strains.