Journal article
Fifteen to Twenty Percent of HIV substitution mutations are associated with recombination
Journal of Virology, Vol.88(7), pp.3837-3849
2014
Abstract
HIV undergoes a high rate of mutation and recombination during reverse transcription, but it is not known whether these events occur independently or are linked mechanistically. Here we use a system of silent marker mutations in HIV and a single round of infection in primary T-lymphocytes, combined with a high-throughput sequencing and mathematical modelling approach to directly estimate the viral 38 recombination and mutation rates. From >7 million nt of sequences from HIV infection, we observe 4801 recombination events and 859 substitution mutations (≈1.51 and 0.12 events per 1000 nt respectively). We use experimental controls to account for PCR-induced and transfection-induced recombination and sequencing error. We find the single cycle virus-induced mutation rate is 4.6 x 10-5 mutations per nt after correction. By sorting our data into recombined and non-recombined sequences, we find a significantly higher mutation rate in recombined regions (p=0.003, Fisher’s exact). We use a permutation approach to eliminate a number of potential confounding factors and confirm that mutation occurs around the site of recombination, and is not simply co-located in the genome. By comparing mutation rates in recombined and non-recombined regions we find that recombination associated mutations account for 15-20% of all mutations occurring during reverse transcription.
Details
- Title
- Fifteen to Twenty Percent of HIV substitution mutations are associated with recombination
- Authors/Creators
- T.E. Schlub (Author/Creator)A.J. Grimm (Author/Creator)R.P. Smyth (Author/Creator)D. Cromer (Author/Creator)A. Chopra (Author/Creator)S. Mallal (Author/Creator)V. Venturi (Author/Creator)C. Waugh (Author/Creator)J. Mak (Author/Creator)M.P. Davenport (Author/Creator)
- Publication Details
- Journal of Virology, Vol.88(7), pp.3837-3849
- Publisher
- American Society for Microbiology
- Identifiers
- 991005541697807891
- Copyright
- © 2014 American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.1243 Integrase
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology