Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.08.28.272351

Quantifying the dynamics of viral recombination during free virus and cell-to-cell transmission in HIV-1 infection

Kreger, J.·Garcia, J.·Komarova, N. L.·Wodarz, D.·Levy, D. N.
View original source ↗Export metadata ↓

Abstract

Recombination has been shown to contribute to HIV-1 evolution in vivo, but the underlying dynamics are extremely complex, depending on the nature of the fitness landscapes and of epistatic interactions. A less well-studied determinant of recombinant evolution is the mode of virus transmission in the cell population. HIV-1 can spread by free virus transmission, resulting largely in singly infected cells, and also by direct cell-to-cell transmission, resulting in the simultaneous infection of cells with multiple viruses. We investigate the contribution of these two transmission pathways to recombinant evolution, by applying mathematical models to in vitro experimental data on the growth of fluorescent reporter viruses under static conditions (where both transmission pathways operate), and under gentle shaking conditions, where cell-to-cell transmission is largely inhibited. The parameterized mathematical models are then used to extrapolate the viral evolutionary dynamics beyond the experimental settings. Assuming a fixed basic reproductive ratio of the virus (independent of transmission pathway), we find that recombinant evolution is fastest if virus spread is driven only by cell-to-cell transmission, and slows down if both transmission pathways operate. Recombinant evolution is slowest if all virus spread occurs through free virus transmission. This is due to cell-to-cell transmission (i) increasing infection multiplicity, (ii) promoting the co-transmission of different virus strains from cell to cell, and (iii) increasing the rate at which point mutations are generated as a result of more reverse transcription events. This work further resulted in the estimation of various parameters that characterize these evolutionary processes. For example, we estimate that during cell-to-cell transmission, an average of 3 viruses successfully integrated into the target cell, which can significantly raise the infection multiplicity compared to free virus transmission. In general, our study points towards the importance of infection multiplicity and cell-to-cell transmission for HIV-evolution.

Source connections

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kreger, J., Garcia, J., Komarova, N. L., Wodarz, D., Levy, D. N.. 2020-08-29. Quantifying the dynamics of viral recombination during free virus and cell-to-cell transmission in HIV-1 infection. https://doi.org/10.1101/2020.08.28.272351

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Ocean current models predict spatial structure for coastal biodiversity

Genomic diversity provides the raw material through which all evolutionary processes occur. Accurately describing how environmental features affect patterns of diversity shows promise in predicting the resilience of populations and entire communities to dynamic environments and novel stressors. Identifying the contribution of purely neutral responses to environmental effects can be difficult, especially across large spatial ranges with many covarying environmental features. Using an individual-based model of larvae carried by ocean currents, we predict patterns of neutral genomic diversity in a passively dispersed coastal species, suggesting large geographic regions of relative homogeneity with ancestry determined by the nearest "upstream" population with limited larval input. The genomic identity that dominates each region sharply transitions at the next such interruption, generating hierarchical structure and violating assumptions of isolation-by-distance. We call these upstream populations "lineage source regions" (LSRs), and we find strong concordance between LSR model predictions and an empirical population genomic survey of a keystone salt marsh mussel (Geukensia demissa). We quantitatively validate model performance and goodness-of-fit, updating baseline predictions of genomic diversity patterns from the classic isolation-by-distance model to this LSR framework. This spatially explicit coastal ancestry model has potential for generalization across passive dispersing species.

evolutionary biology↗
bioRxiv2026

TaxaAudit: A statistical model of consensus in phylogenetics identifies non-monophyletic taxa

Interpreting variation in genes and traits across species requires understanding their evolutionary relationships. Taxonomic hierarchies provide a practical approximation of the tree of life, with the NCBI taxonomy linking this framework directly to public sequence data. Some named groups, however, are not evolutionary clades, and recognizing these exceptions requires knowledge scattered across the phylogenetics literature. Here we introduce TaxaAudit, a statistical model that identifies taxonomic groups whose monophyly is repeatedly contradicted by published phylogenies. The model accounts for background taxonomic conflict and the ability of each study's species sampling to expose non-monophyly. Applied to 5,865 molecular phylogenies from TimeTree, TaxaAudit flagged 516 NCBI taxa at family rank and below for significant recurrent contradiction of monophyly. Excluding these taxa's monophyly requirements improved the taxonomy's agreement with independent phylogenomic reference trees and phylogenies withheld from discovery. Flagged taxa were also 3.61 times as likely as matched controls to have their monophyly challenged in publications outside the discovery set. In tree-inference experiments, excluding these monophyly constraints improved agreement with reference phylogenies relative to enforcing the unmodified taxonomy. By identifying groups whose monophyly should not be assumed, TaxaAudit lets researchers draw on published phylogenetic knowledge without reviewing the specialist literature for every taxon. This supports broader use of the NCBI taxonomy as an evolutionary framework for biological comparisons.

evolutionary biology↗
bioRxiv2026

Shared landscape, divergent genomes: Comparative population genomics of co-occurring flora in an isolated Australian mountain range

Understanding how landscape heterogeneity shapes genomic variation is key to conserving biodiversity and evolutionary potential. Yet conservation genomics is typically conducted at the single species level, limiting our ability to identify shared genomic patterns or understand how co-occurring taxa differ in their response to common environmental gradients. We assessed spatial patterns of genomic variation and their associations with geographic and environmental features among populations of nine co-existing plant species with contrasting life-histories and ecological traits across Gariwerd, a threatened biodiversity hotspot in south-eastern Australia. All species exhibited weak overall genetic structure, although the magnitude and spatial distribution of differentiation varied among species. Despite this variation, broadly consistent spatial trends were apparent, with higher genomic divergence largely concentrated in central zones and higher genomic diversity localised in southern regions of the landscape. Significant associations between genetic differentiation and geographic distance were observed in three species, while another species showed associations with environmental distance. These findings demonstrate that coexisting species can show overlapping spatial patterns in genomic variation while differing markedly in their associations with geographic and environmental variation across the same landscape. This comparative approach provides a basis for spatial prioritisation and conservation planning, while highlighting the complex eco-evolutionary processes operating across heterogeneous landscapes.

evolutionary biology↗