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Title: Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection

Journal Article · · PLoS Pathogens
 [1];  [1];  [2];  [1];  [3];  [1];  [4];  [1];  [5];  [6];  [7];  [3];  [1]
  1. Northwestern University, Chicago, IL (United States)
  2. University of California, San Diego, CA (United States)
  3. King's College, London (United Kingdom)
  4. University of Manchester (United Kingdom)
  5. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
  6. University of California, San Diego, CA (United States); Veterans Affairs San Diego Healthcare System, San Diego, CA (United States)
  7. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Santa Fe Institute (SFI), Santa Fe, NM (United States)
+ Show Author Affiliations

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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); California HIV Research Program (CHRP); U.K. Medical Research Council; HIV Immune Network Team Program
Grant/Contract Number:
AC52-06NA25396; AI43638; AI074621; AI070072; AI035039; RN07-SD-702; G1000196; P01AI090935
OSTI ID:
1627909
Journal Information:
PLoS Pathogens, Vol. 10, Issue 7; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (13)

Impact of suboptimal APOBEC3G neutralization on the emergence of HIV drug resistance in humanized mice journal January 2019
Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation journal May 2016
Recent advances in understanding HIV evolution journal January 2017
Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region journal December 2017
Estimating the mutational fitness effects distribution during early HIV infection journal July 2018
Increasing the CpG dinucleotide abundance in the HIV-1 genomic RNA inhibits viral replication journal November 2017
Persistent HIV-1 replication maintains the tissue reservoir during therapy journal January 2016
Prediction of HIV-1 and HIV-2 proteins by using Chou’s pseudo amino acid compositions and different classifiers journal February 2018
HIV-1 and interferons: who's interfering with whom? journal April 2015
Genetic and mechanistic basis for APOBEC3H alternative splicing, retrovirus restriction, and counteraction by HIV-1 protease journal October 2018
Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B journal December 2016
Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G journal November 2017
A Canonical Correlation Analysis of AIDS Restriction Genes and Metabolic Pathways Identifies Purine Metabolism as a Key Cooperator journal January 2016

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59 BASIC BIOLOGICAL SCIENCES
HIV-1
microbial mutation
sequence alignment
haplotypes
substitution mutation
nucleotide sequencing
nucleotides
viral evolution