Nature Structural & Molecular Biology11, 435 - 442 (2004)
Published online: 18 April 2004; | doi:10.1038/nsmb758
Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome
Qin Yu1, Renate König1, Satish Pillai2, Kristopher Chiles1, Mary Kearney3, Sarah Palmer3, Douglas Richman4, 5, John M Coffin3
& Nathaniel R Landau1
1
Infectious Disease Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California
92037, USA.
2
Division of Biological Sciences, University of California, San Diego, La Jolla, California
92093-0679, USA.
3
HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland
21702, USA.
4
Departments of Pathology and Medicine, University of California, San Diego, La Jolla, California
92093-0679, USA.
5
Veterans Administration, San Diego Healthcare System, San Diego, California
92161, USA.
Correspondence should be addressed to Nathaniel R Landau landau@salk.edu
HIV-1 deleted for the vif accessory gene encapsidates the cellular cytidine deaminase APOBEC3G. Upon infection, the encapsidated APOBEC3G induces GA mutations in the viral reverse transcripts. The GA mutations result either from CU 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 CT 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 CT mutations.
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