Abstract
BackgroundDeep sequencing provides the basis for analysis of biodiversity of taxonomically similar organisms in an environment. While extensively applied to microbiome studies, population genetics studies of viruses are limited. To define the scope of HIV-1 population biodiversity within infected individuals, a suite of phylogenetic and population genetic algorithms was applied to HIV-1 envelope hypervariable domain 3 (Env V3) within peripheral blood mononuclear cells from a group of perinatally HIV-1 subtype B infected, therapy-naïve children.ResultsBiodiversity of HIV-1 Env V3 quasispecies ranged from about 70 to 270 unique sequence clusters across individuals. Viral population structure was organized into a limited number of clusters that included the dominant variants combined with multiple clusters of low frequency variants. Next generation viral quasispecies evolved from low frequency variants at earlier time points through multiple non-synonymous changes in lineages within the evolutionary landscape. Minor V3 variants detected as long as four years after infection co-localized in phylogenetic reconstructions with early transmitting viruses or with subsequent plasma virus circulating two years later.ConclusionsDeep sequencing defines HIV-1 population complexity and structure, reveals the ebb and flow of dominant and rare viral variants in the host ecosystem, and identifies an evolutionary record of low-frequency cell-associated viral V3 variants that persist for years. Bioinformatics pipeline developed for HIV-1 can be applied for biodiversity studies of virome populations in human, animal, or plant ecosystems.
Highlights
Deep sequencing provides the basis for analysis of biodiversity of taxonomically similar organisms in an environment
Biodiversity of Human immunodeficiency virus type 1 (HIV-1) quasispecies Biodiversity is evaluated by rarefaction analysis and defined as the number of operational taxonomic units (OTU) within a population [17,18,21,23,24,25,26]
HIV-1 envelope hypervariable domain 3 (Env V3) pyrosequences within each sample were clustered over a range of pairwise genetic distances from 0% to 10% to compare viral populations among individuals (Figure 1)
Summary
Deep sequencing provides the basis for analysis of biodiversity of taxonomically similar organisms in an environment. Assessments of biodiversity from deep sequencing data provide unprecedented views of the richness of immune loci in primates, zebra fish, and humans [17,18,26] or the complexity of microbiomes independent of an ability to culture microorganisms [21,24,25,29]. Biodiversity defines complexity within populations that extend beyond evaluations of diversity based on pairwise genetic distance, the major approach for analysis of small data sets of HIV-1 sequences from infected individuals [30,31]. Biodiversity within HIV-1 populations might reflect host environments, infection by circulating recombinant forms of HIV-1 or co-infection by multiple subtypes, and provide unique and sensitive biomarkers for changes in viral populations. Structure of HIV-1 quasispecies, or the frequency distribution of viral variants within individuals, may reveal the potential for viral populations to evolve within a fitness landscape and contribute to viral persistence [4,32,33,34]
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