Dataset Information

Phylogenetic patterns recover known HIV epidemiological relationships and reveal common transmission of multiple variants.

ABSTRACT: The growth of human immunodeficiency virus (HIV) sequence databases resulting from drug resistance testing has motivated efforts using phylogenetic methods to assess how HIV spreads1-4. Such inference is potentially both powerful and useful for tracking the epidemiology of HIV and the allocation of resources to prevention campaigns. We recently used simulation and a small number of illustrative cases to show that certain phylogenetic patterns are associated with different types of epidemiological linkage5. Our original approach was later generalized for large next-generation sequencing datasets and implemented as a free computational pipeline6. Previous work has claimed that direction and directness of transmission could not be established from phylogeny because one could not be sure that there were no intervening or missing links involved7-9. Here, we address this issue by investigating phylogenetic patterns from 272 previously identified HIV transmission chains with 955 transmission pairs representing diverse geography, risk groups, subtypes, and genomic regions. These HIV transmissions had known linkage based on epidemiological information such as partner studies, mother-to-child transmission, pairs identified by contact tracing, and criminal cases. We show that the resulting phylogeny inferred from real HIV genetic sequences indeed reveals distinct patterns associated with direct transmission contra transmissions from a common source. Thus, our results establish how to interpret phylogenetic trees based on HIV sequences when tracking who-infected-whom, when and how genetic information can be used for improved tracking of HIV spread. We also investigate limitations that stem from limited sampling and genetic time-trends in the donor and recipient HIV populations.

SUBMITTER: Leitner T

PROVIDER: S-EPMC6442454 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Phylogenetic patterns recover known HIV epidemiological relationships and reveal common transmission of multiple variants.

Leitner Thomas T Romero-Severson Ethan E

Nature microbiology 20180730 9

The growth of human immunodeficiency virus (HIV) sequence databases resulting from drug resistance testing has motivated efforts using phylogenetic methods to assess how HIV spreads<sup>1-4</sup>. Such inference is potentially both powerful and useful for tracking the epidemiology of HIV and the allocation of resources to prevention campaigns. We recently used simulation and a small number of illustrative cases to show that certain phylogenetic patterns are associated with different types of epi ...[more]

PMID: 30061758

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Project description:Phylogenetic analyses are increasingly used in attempts to clarify transmission patterns of human immunodeficiency virus type 1 (HIV-1), but there is a continuing discussion about their validity because convergent evolution and transmission of minor HIV variants may obscure epidemiological patterns. Here we have studied a unique HIV-1 transmission cluster consisting of nine infected individuals, for whom the time and direction of each virus transmission was exactly known. Most of the transmissions occurred between 1981 and 1983, and a total of 13 blood samples were obtained approximately 2-12 years later. The p17 gag and env V3 regions of the HIV-1 genome were directly sequenced from uncultured lymphocytes. A true phylogenetic tree was constructed based on the knowledge about when the transmissions had occurred and when the samples were obtained. This complex, known HIV-1 transmission history was compared with reconstructed molecular trees, which were calculated from the DNA sequences by several commonly used phylogenetic inference methods [Fitch-Margoliash, neighbor-joining, minimum-evolution, maximum-likelihood, maximum-parsimony, unweighted pair group method using arithmetic averages (UPGMA), and a Fitch-Margoliash method assuming a molecular clock (KITSCH)]. A majority of the reconstructed trees were good estimates of the true phylogeny; 12 of 13 taxa were correctly positioned in the most accurate trees. The choice of gene fragment was found to be more important than the choice of phylogenetic method and substitution model. However, methods that are sensitive to unequal rates of change performed more poorly (such as UPGMA and KITSCH, which assume a constant molecular clock). The rapidly evolving V3 fragment gave better reconstructions than p17, but a combined data set of both p17 and V3 performed best. The accuracy of the phylogenetic methods justifies their use in HIV-1 research and argues against convergent evolution and selective transmission of certain virus variants.

Dataset Information

Phylogenetic patterns recover known HIV epidemiological relationships and reveal common transmission of multiple variants.

Publications

Phylogenetic patterns recover known HIV epidemiological relationships and reveal common transmission of multiple variants.

Similar Datasets

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