Recombination smooths the time-signal disrupted by latency in within-host HIV phylogenies

Journal Article · Sat May 20 00:00:00 EDT 2023 · Virus Evolution

DOI:https://doi.org/10.1093/ve/vead032· OSTI ID:1975645

Castro, Lauren Ann  ^[1]; Leitner, Thomas Kenneth  ^[2]; Romero-Severson, Ethan  ^[2]

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1. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Univ. of Texas, Austin, TX (United States)
2. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Within-host HIV evolution involves several features that may disrupt standard phylogenetic reconstruction. One important feature is re-activation of latently integrated provirus, which has the potential to disrupt the temporal signal, leading to variation in the branch lengths and apparent evolutionary rates in a tree. Yet, real within-host HIV phylogenies tend to show clear, ladder-like trees structured by the time of sampling. Another important feature is recombination, which violates the fundamental assumption that evolutionary history can be represented by a single bifurcating tree. Thus, recombination complicates the within-host HIV dynamic by mixing genomes and creating evolutionary loop structures that cannot be represented in bifurcating trees. In this paper, we develop a coalescent-based simulator of within-host HIV evolution that includes latency, recombination, and effective population size dynamics that allows us to study the relationship between the true, complex genealogy of within-host HIV evolution, encoded as an Ancestral Recombination Graph (ARG), and the observed phylogenetic tree. To compare our ARG results to the familiar phylogeny format, we calculate the expected bifurcating tree after decomposing the ARG into all unique site trees, their combined distance matrix, and the overall corresponding bifurcating tree. While latency and recombination separately disrupt the phylogenetic signal, remarkably, we find that recombination recovers the temporal signal of within-host HIV evolution caused by latency by mixing fragments of old, latent genomes into the contemporary population. In effect, recombination averages over extant heterogeneity, whether it stems from mixed time-signals or population bottlenecks. Further, we establish that the signals of latency and recombination can be observed in phylogenetic trees despite being an incorrect representation of the true evolutionary history. Using an Approximate Bayesian Computation method, we develop a set of statistical probes to tune our simulation model to nine longitudinally-sampled within-host HIV phylogenies. Because ARGs are exceedingly difficult to infer from real HIV data, our simulation system allows investigating effects of latency, recombination, and population size bottlenecks by matching decomposed ARGs to real data as observed in standard phylogenies.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH)
• Grant/Contract Number: 89233218CNA000001; R01AI087520
• OSTI ID: 1975645
• Report Number(s): LA-UR-22-21449
• Journal Information: Virus Evolution, Vol. 9, Issue 1; ISSN 2057-1577
• Publisher: Oxford University Press
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biological Science