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Sequence editing by Apolipoprotein B RNA-editing catalytic component-B and epidemiological surveillance of transmitted HIV-1 drug resistance

Gifford, Robert Ja; Rhee, Soo-Yona; Eriksson, Nicolasb; Liu, Tommy Fa; Kiuchi, Marka; Das, Amar Kc; Shafer, Robert Wa

Erratum

A typographical error was published in the article ‘Sequence editing by Apolipoprotein B RNA-editing catalytic component and epidemiological surveillance of transmitted HIV-1 drug resistance?’ by Gifford RJ et al.[1] which appeared on pp 717–25 of AIDS, Volume 22, issue 6.

The title was mis-spelt. It was published as ‘Sequence editing by Apolipoprotein B RNA-editing catalytic component-B and epidemiological surveillance of transmitted HIV-1 drug resistance.’ It should have read ‘Sequence editing by Apolipoprotein B RNA-editing catalytic component and epidemiological surveillance of transmitted HIV-1 drug resistance.’

AIDS. 22(16):2225, October 18, 2008.

doi: 10.1097/QAD.0b013e3282f5e07a
Clinical Science

Design: Promiscuous guanine (G) to adenine (A) substitutions catalysed by apolipoprotein B RNA-editing catalytic component (APOBEC) enzymes are observed in a proportion of HIV-1 sequences in vivo and can introduce artifacts into some genetic analyses. The potential impact of undetected lethal editing on genotypic estimation of transmitted drug resistance was assessed.

Methods: Classifiers of lethal, APOBEC-mediated editing were developed by analysis of lentiviral pol gene sequence variation and evaluated using control sets of HIV-1 sequences. The potential impact of sequence editing on genotypic estimation of drug resistance was assessed in sets of sequences obtained from 77 studies of 25 or more therapy-naive individuals, using mixture modelling approaches to determine the maximum likelihood classification of sequences as lethally edited as opposed to viable.

Results: Analysis of 6437 protease and reverse transcriptase sequences from therapy-naive individuals using a novel classifier of lethal, APOBEC3G-mediated sequence editing, the polypeptide-like 3G (APOBEC3G)-mediated defectives (A3GD) index', detected lethal editing in association with spurious ‘transmitted drug resistance’ in nearly 3% of proviral sequences obtained from whole blood and 0.2% of samples obtained from plasma.

Conclusion: Screening for lethally edited sequences in datasets containing a proportion of proviral DNA, such as those likely to be obtained for epidemiological surveillance of transmitted drug resistance in the developing world, can eliminate rare but potentially significant errors in genotypic estimation of transmitted drug resistance.

From the aDivision of Infectious Diseases, Department of Medicine, USA

bDepartment of Biostatistics, USA

cDivision of Biomedical Informatics, Department of Medicine, Stanford University, Stanford, California, USA.

Correspondence to Dr Robert Gifford, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA. Tel: +1 650 725 2946; fax: +1 650 725 2088; e-mail: rjmg@stanford.edu.

© 2008 Lippincott Williams & Wilkins, Inc.