Insights into the motif preference of APOBEC3 enzymes

PLoS One. 2014 Jan 31;9(1):e87679. doi: 10.1371/journal.pone.0087679. eCollection 2014.

Abstract

We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3' end (in +1 and +2 positions) were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3'polypurine tracts (PPTs) which remain double stranded during the HIV reverse transcription. GGGG motifs outside the PPTs were also disfavoured. The motifs GGAG and GAGG were also found to be disfavoured targets for APOBEC3. The motif-dependent mutation of G within the HIV genome by members of the APOBEC3 family other than APOBEC3G was limited to GA→AA changes. The results did not show evidence of other types of context dependent G-to-A changes in the HIV genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase
  • CpG Islands*
  • Cytidine Deaminase / chemistry*
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism
  • DNA, Viral / chemistry*
  • Genome, Viral
  • HIV-1 / chemistry*
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • Humans
  • Point Mutation
  • Substrate Specificity

Substances

  • DNA, Viral
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase

Grants and funding

This work is funded by the Australian National Health and Medical Research Council (NHMRC). DE is funded by an Early Career Fellowship from NHMRC. MPD is a senior Research Fellow funded by NHMRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.