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Updated: May 12, 2026

13:07
Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
Published on: January 30, 2019
Getting to the root of HIV transmitted founder virus sequences
Bradley R Jones1, Zabrina L Brumme2,3, Eric Hunter4,5
1Department of Mathematics, Simon Fraser University, Burnaby, Canada.
Virus Evolution
|May 11, 2026
Summary
Reconstructing transmitted founder virus sequences from proviral DNA is challenging. While proviral sequences offer a potential archive, current methods show limited success, indicating a need for new approaches to accurately estimate early viral evolution.
Area of Science:
- Virology
- Evolutionary Biology
- Bioinformatics
Background:
- Determining the transmitted founder virus sequence is crucial for understanding early viral dynamics and evolution.
- Traditional methods for founder virus reconstruction require early or longitudinal samples, which are difficult to obtain.
- Human immunodeficiency virus (HIV) integrates into host cells, creating a proviral archive that may preserve evolutionary history.
Purpose of the Study:
- To investigate the feasibility of using proviral sequences for ancestral sequence reconstruction to estimate transmitted founder virus sequences in HIV infection.
- To evaluate the accuracy of different phylogenetic methods for root placement and founder virus sequence reconstruction from proviral DNA.
Main Methods:
- Analysis of a dataset of 12 participants with early HIV sequences and longitudinal proviral sequences collected before and after suppressive therapy.
- Application of various phylogenetic methods for ancestral sequence reconstruction and root placement using proviral sequences.
- Comparison of reconstructed founder virus sequences with known early sequences to assess accuracy.
Main Results:
- Limited success was achieved in reconstructing founder virus sequences using existing ancestral sequence reconstruction and rooting methods from proviral DNA.
- Reconstruction accuracy was higher when participants' proviral sequences were more similar to their estimated founder sequences.
- Phylogenetic methods showed variable performance in root placement and founder sequence estimation.
Conclusions:
- Reconstructing transmitted founder virus sequences from integrated proviral DNA using current phylogenetic methods is challenging.
- The similarity between proviral and founder sequences influences reconstruction accuracy.
- Development of novel methods is necessary for effective founder virus sequence estimation from proviral archives.
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