Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection

• Published in: PLoS pathogens 2014-07, Vol.10 (7), p.e1004281
• Main Authors: Kim, Eun-Young, Lorenzo-Redondo, Ramon, Little, Susan J, Chung, Yoon-Seok, Phalora, Prabhjeet K, Maljkovic Berry, Irina, Archer, John, Penugonda, Sudhir, Fischer, Will, Richman, Douglas D, Bhattacharya, Tanmoy, Malim, Michael H, Wolinsky, Steven M
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - genetics; Aminohydrolases - genetics; APOBEC Deaminases; APOBEC-3G Deaminase; Base Sequence; BASIC BIOLOGICAL SCIENCES; Binding sites; Biological Evolution; Biology and Life Sciences; Cellular proteins; Colleges & universities; Cytidine Deaminase - genetics; Cytosine Deaminase - genetics; Defense mechanisms; Deoxyribonucleic acid; DNA; DNA, Viral - genetics; Editing; Error correction & detection; Gene mutations; Genes; Genetic aspects; Genetic diversity; Genetic Variation - genetics; Genome, Viral; Genomes; Haplotypes; Health aspects; High-Throughput Nucleotide Sequencing; HIV; HIV infection; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; HIV-1; HIV-1 - genetics; Human immunodeficiency virus; Humans; Infections; Medicine and Health Sciences; microbial mutation; Molecular Sequence Data; Mutation; Mutation - genetics; nucleotide sequencing; nucleotides; Peptides; Phylogeny; Physiological aspects; Polymerase Chain Reaction; Proteins; RNA polymerase; sequence alignment; Sequence Homology, Nucleic Acid; substitution mutation; viral evolution; Virus Replication - genetics
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1004281

Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A) mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1) cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA)-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection.