A Highly Defective HIV-1 Group O Provirus: Evidence for the Role of Local Sequence Determinants in G → A Hypermutation during Negative-Strand Viral DNA Synthesis

47Citations
Citations of this article
16Readers
Mendeley users who have this article in their library.

Abstract

The sequence of 2350 nucleotides in the env and IN regions of a group O HIV-1 genome which is hypermutated throughout its entirety was compared to the equivalent sequence of a nonhypermutated genome from the same isolate. Almost 30% of G residues were affected by G → A transitions. As previously reported, transitions occurred mainly at GpA and GpG dinucleotides, with a marked preference for changes of the 5′-proximal G residues in poly(G) stretches. Inspection of the sequences around the hypermutation sites revealed no bias when the mutation was at the 5′ G residue of a GpG dinucleotide. In contrast, a preferred context for hypermutation at the 3′ G (or at single G residues) could be defined. In addition to a preference for A residues immediately downstream of hypermutated 3′ G residues, C residues were underrepresented in these positions. The observed context fits well with a model whereby G → A mutation occurs by a combination of dislocation mutagenesis at GpA dinucleotides and direct misincorporation of dTTP at the 5′ G of GpG dinucleotides. Furthermore, both runs of six G residues present in the polypurine tracts (PPTs) had escaped hypermutation, despite the fact that 95% of runs of three G residues contained at least one G → A transition. This finding suggests that genomes with hypermutated PPT motifs had been selected against and provides direct evidence that hypermutation occurs during negative-strand DNA synthesis. © 1995 Academic Press. All rights reserved.

Cite

CITATION STYLE

APA

Borman, A. M., Quillent, C., Charneau, P., Kean, K. M., & Clavel, F. (1995). A Highly Defective HIV-1 Group O Provirus: Evidence for the Role of Local Sequence Determinants in G → A Hypermutation during Negative-Strand Viral DNA Synthesis. Virology, 208(2), 601–609. https://doi.org/10.1006/viro.1995.1191

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free