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Fifteen to twenty percent of HIV substitution mutations are associated with recombination

Schlub, Timothy E., Grimm, Andrew J., Smyth, Redmond P., Cromer, Deborah, Chopra, Abha, Mallal, Simon, Venturi, Vanessa, Waugh, Caryll, Mak, Johnson and Davenport, Miles P. 2014, Fifteen to twenty percent of HIV substitution mutations are associated with recombination, Journal of virology, vol. 88, no. 7, pp. 3837-3849, doi: 10.1128/JVI.03136-13.

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Title Fifteen to twenty percent of HIV substitution mutations are associated with recombination
Author(s) Schlub, Timothy E.
Grimm, Andrew J.
Smyth, Redmond P.
Cromer, Deborah
Chopra, Abha
Mallal, Simon
Venturi, Vanessa
Waugh, Caryll
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Davenport, Miles P.
Journal name Journal of virology
Volume number 88
Issue number 7
Start page 3837
End page 3849
Total pages 13
Publisher American Society for Microbiology
Place of publication Washington, D.C.
Publication date 2014-04
ISSN 1098-5514
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Virology
IMMUNODEFICIENCY-VIRUS TYPE-1
REVERSE-TRANSCRIPTASE
STRAND TRANSFER
IN-VITRO
GENETIC-RECOMBINATION
INTERSUBTYPE RECOMBINATION
HOMOLOGOUS RECOMBINATION
RETROVIRAL RECOMBINATION
PROMOTES RECOMBINATION
VIRAL REPLICATION
Summary HIV undergoes high rates of mutation and recombination during reverse transcription, but it is not known whether these events occur independently or are linked mechanistically. Here we used 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 modeling approach to directly estimate the viral recombination and mutation rates. From >7 million nucleotides (nt) of sequences from HIV infection, we observed 4,801 recombination events and 859 substitution mutations (≈1.51 and 0.12 events per 1,000 nt, respectively). We used experimental controls to account for PCR-induced and transfection-induced recombination and sequencing error. We found that the single-cycle virus-induced mutation rate is 4.6 × 10(-5) mutations per nt after correction. By sorting of our data into recombined and nonrecombined sequences, we found a significantly higher mutation rate in recombined regions (P = 0.003 by Fisher's exact test). We used 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 colocated in the genome. By comparing mutation rates in recombined and nonrecombined regions, we found that recombination-associated mutations account for 15 to 20% of all mutations occurring during reverse transcription.
Language eng
DOI 10.1128/JVI.03136-13
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, American Society for Microbiology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30070527

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.