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Open Access Research

APOBEC3G and APOBEC3F rarely co-mutate the same HIV genome

Diako Ebrahimi, Firoz Anwar and Miles P Davenport*

Author Affiliations

Centre for Vascular Research, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

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Retrovirology 2012, 9:113  doi:10.1186/1742-4690-9-113

Published: 20 December 2012

Abstract

Background

The human immune proteins APOBEC3G and APOBEC3F (hA3G and hA3F) induce destructive G-to-A changes in the HIV genome, referred to as ‘hypermutation’. These two proteins co-express in human cells, co-localize to mRNA processing bodies and might co-package into HIV virions. Therefore they are expected to also co-mutate the HIV genome. Here we investigate the mutational footprints of hA3G and hA3F in a large population of full genome HIV-1 sequences from naturally infected patients to uniquely identify sequences hypermutated by either or both of these proteins. We develop a method of identification based on the representation of hA3G and hA3F target and product motifs that does not require an alignment to a parental/consensus sequence.

Results

Out of nearly 100 hypermutated HIV-1 sequences only one sequence from the HIV-1 outlier group showed clear signatures of co-mutation by both proteins. The remaining sequences were affected by either hA3G or hA3F.

Conclusion

Using a novel method of identification of HIV sequences hypermutated by the hA3G and hA3F enzymes, we report a very low rate of co-mutation of full-length HIV sequences, and discuss the potential mechanisms underlying this.

Keywords:
Hypermutated HIV; APOBEC3G; APOBEC3F; Motif representation; G-to-A mutation signature