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Nat Struct Mol Biol. 2004 May;11(5):435-42. Epub 2004 Apr 18.

Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome.

Author information

1
Infectious Disease Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

Abstract

HIV-1 deleted for the vif accessory gene encapsidates the cellular cytidine deaminase APOBEC3G. Upon infection, the encapsidated APOBEC3G induces G-->A mutations in the viral reverse transcripts. The G-->A mutations result either from C-->U deamination of the minus strand or deamination of both strands followed by repair of the plus strand. We report here that minus-strand deamination occurred over the length of the virus genome, preferentially at CCCA sequences, with a graded frequency in the 5'-->3' direction. APOBEC3G induced previously undetected C-->T mutations in the 5' U3 and the primer-binding site, both of which become transiently single-stranded during reverse transcription. In vitro, APOBEC3G bound and deaminated single-stranded DNA (ssDNA) but not double-stranded DNA (dsDNA) or DNA-RNA hybrids. We propose that the requirement for ssDNA accounts for the minus-strand mutations, the 5'-->3' graded frequency of deamination and the rare C-->T mutations.

PMID:
15098018
DOI:
10.1038/nsmb758
[Indexed for MEDLINE]

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