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Accurately measuring recombination between closely related HIV-1 genomes

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journal contribution
posted on 2010-04-01, 00:00 authored by T Schlub, R Smyth, A Grimm, Johnson Mak, M Davenport
Retroviral recombination is thought to play an important role in the generation of immune escape and multiple drug resistance by shuffling pre-existing mutations in the viral population. Current estimates of HIV-1 recombination rates are derived from measurements within reporter gene sequences or genetically divergent HIV sequences. These measurements do not mimic the recombination occurring in vivo, between closely related genomes. Additionally, the methods used to measure recombination make a variety of assumptions about the underlying process, and often fail to account adequately for issues such as co-infection of cells or the possibility of multiple template switches between recombination sites. We have developed a HIV-1 marker system by making a small number of codon modifications in gag which allow recombination to be measured over various lengths between closely related viral genomes. We have developed statistical tools to measure recombination rates that can compensate for the possibility of multiple template switches. Our results show that when multiple template switches are ignored the error is substantial, particularly when recombination rates are high, or the genomic distance is large. We demonstrate that this system is applicable to other studies to accurately measure the recombination rate and show that recombination does not occur randomly within the HIV genome.

History

Journal

PLoS computational biology

Volume

6

Pagination

1 - 11

Location

San Francisco, Calif.

Open access

  • Yes

ISSN

1553-734X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2010, Public Library of Science