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

Journal Article · · PLoS Pathogens
 [1];  [2];  [3];  [2];  [4];  [2];  [5];  [2];  [6];  [7];  [8];  [4];  [2]
  1. Northwestern University, Chicago, IL (United States); DOE/OSTI
  2. Northwestern University, Chicago, IL (United States)
  3. University of California, San Diego, CA (United States)
  4. King's College, London (United Kingdom)
  5. University of Manchester (United Kingdom)
  6. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
  7. University of California, San Diego, CA (United States); Veterans Affairs San Diego Healthcare System, San Diego, CA (United States)
  8. 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
OSTI ID:
1627909
Journal Information:
PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 7 Vol. 10; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (67)

Dollo on Dollo's law: Irreversibility and the status of evolutionary laws journal January 1970
Enhanced CD4+ T-Cell Recovery with Earlier HIV-1 Antiretroviral Therapy journal January 2013
MUSCLE: multiple sequence alignment with high accuracy and high throughput journal March 2004
APOBEC proteins and intrinsic resistance to HIV-1 infection journal November 2008
A multi-site study using high-resolution HLA genotyping by next generation sequencing journal February 2011
Conserved Footprints of APOBEC3G on Hypermutated Human Immunodeficiency Virus Type 1 and Human Endogenous Retrovirus HERV-K(HML2) Sequences journal June 2008
Suppression of HIV-1 Infection by APOBEC3 Proteins in Primary Human CD4 + T Cells Is Associated with Inhibition of Processive Reverse Transcription as Well as Excessive Cytidine Deamination journal November 2012
Different Mutagenic Potential of HIV-1 Restriction Factors APOBEC3G and APOBEC3F Is Determined by Distinct Single-Stranded DNA Scanning Mechanisms journal March 2014
Viral population estimation using pyrosequencing text January 2007
Dollo on Dollo's law: Irreversibility and the status of evolutionary laws journal January 1970
Lack of evidence for proofreading mechanisms associated with an RNA virus polymerase journal December 1992
HIV-1 Sequence Variation journal February 2001
DNA Deamination Mediates Innate Immunity to Retroviral Infection journal June 2003
HIV-1 Vif Adaptation to Human APOBEC3H Haplotypes journal October 2013
APOBEC3F Properties and Hypermutation Preferences Indicate Activity against HIV-1 In Vivo journal August 2004
Cytidine Deamination of Retroviral DNA by Diverse APOBEC Proteins journal August 2004
The evolutionary rate dynamically tracks changes in HIV-1 epidemics: Application of a simple method for optimizing the evolutionary rate in phylogenetic trees with longitudinal data journal December 2009
Multiple APOBEC3 Restriction Factors for HIV-1 and One Vif to Rule Them All journal March 2014
APOBEC-mediated viral restriction: not simply editing? journal March 2007
Cellular immune responses to HIV journal April 2001
Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection journal December 2011
Mutational and fitness landscapes of an RNA virus revealed through population sequencing journal November 2013
The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif journal October 2003
Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome journal April 2004
A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins journal May 2004
Enhanced CD4+ T-Cell Recovery with Earlier HIV-1 Antiretroviral Therapy journal January 2013
Cytidine deamination induced HIV-1 drug resistance journal April 2008
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection journal May 2008
Improved tools for biological sequence comparison. journal April 1988
The molecular clock of HIV-1 unveiled through analysis of a known transmission history journal September 1999
A Simple, Fast, and Accurate Algorithm to Estimate Large Phylogenies by Maximum Likelihood journal October 2003
Approximate Likelihood-Ratio Test for Branches: A Fast, Accurate, and Powerful Alternative journal August 2006
The antiviral factor APOBEC3G improves CTL recognition of cultured HIV-infected T cells journal December 2009
Datamonkey: rapid detection of selective pressure on individual sites of codon alignments journal February 2005
Not So Different After All: A Comparison of Methods for Detecting Amino Acid Sites Under Selection journal February 2005
Bayesian Phylogenetics with BEAUti and the BEAST 1.7 journal February 2012
APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase journal April 2004
Twin gradients in APOBEC3 edited HIV-1 DNA reflect the dynamics of lentiviral replication journal September 2006
High throughput HLA genotyping using 454 sequencing and the Fluidigm Access Array™ system for simplified amplicon library preparation: High throughput HLA 454 sequencing using the Fluidigm Access Array™ system journal February 2013
Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-SCF Complex journal November 2003
Timing the Ancestor of the HIV-1 Pandemic Strains journal June 2000
Conserved Footprints of APOBEC3G on Hypermutated Human Immunodeficiency Virus Type 1 and Human Endogenous Retrovirus HERV-K(HML2) Sequences journal June 2008
HIV-1 Replication and APOBEC3 Antiviral Activity Are Not Regulated by P Bodies journal August 2012
Polymorphism in Human APOBEC3H Affects a Phenotype Dominant for Subcellular Localization and Antiviral Activity journal June 2011
Human APOBEC3G-Mediated Editing Can Promote HIV-1 Sequence Diversification and Accelerate Adaptation to Selective Pressure journal July 2010
Polymorphisms and Splice Variants Influence the Antiretroviral Activity of Human APOBEC3H journal October 2008
Analysis of Human APOBEC3H Haplotypes and Anti-Human Immunodeficiency Virus Type 1 Activity journal January 2011
APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different Mechanisms journal March 2010
Suppression of HIV-1 Infection by APOBEC3 Proteins in Primary Human CD4 + T Cells Is Associated with Inhibition of Processive Reverse Transcription as Well as Excessive Cytidine Deamination journal November 2012
Human and Rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H Demonstrate a Conserved Capacity To Restrict Vif-Deficient HIV-1 journal August 2011
Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. journal January 1995
Human Immunodeficiency Virus Type 1 DNA Sequences Genetically Damaged by Hypermutation Are Often Abundant in Patient Peripheral Blood Mononuclear Cells and May Be Generated during Near-Simultaneous Infection and Activation of CD4+ T Cells journal September 2001
Selective Escape from CD8+ T-Cell Responses Represents a Major Driving Force of Human Immunodeficiency Virus Type 1 (HIV-1) Sequence Diversity and Reveals Constraints on HIV-1 Evolution journal November 2005
The APOBEC3 Cytidine Deaminases: An Innate Defensive Network Opposing Exogenous Retroviruses and Endogenous Retroelements journal April 2008
Analysis of high-depth sequence data for studying viral diversity: a comparison of next generation sequencing platforms using Segminator II journal March 2012
HIV-1 Vif, APOBEC, and Intrinsic Immunity journal January 2008
Viral Population Estimation Using Pyrosequencing journal May 2008
APOBEC3G-Induced Hypermutation of Human Immunodeficiency Virus Type-1 Is Typically a Discrete “All or Nothing” Phenomenon journal March 2012
Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing journal August 2010
Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities journal July 2012
Natural Variation in Vif: Differential Impact on APOBEC3G/3F and a Potential Role in HIV-1 Diversification journal January 2005
Likely Role of APOBEC3G-Mediated G-to-A Mutations in HIV-1 Evolution and Drug Resistance journal April 2009
HIV Evolution in Early Infection: Selection Pressures, Patterns of Insertion and Deletion, and the Impact of APOBEC journal May 2009
Massive APOBEC3 Editing of Hepatitis B Viral DNA in Cirrhosis journal May 2010
Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection journal February 2011
Comparison of SIV and HIV-1 Genomic RNA Structures Reveals Impact of Sequence Evolution on Conserved and Non-Conserved Structural Motifs journal April 2013
Retroelements versus APOBEC3 family members: No great escape from the magnificent seven journal January 2012

Cited By (13)

Persistent HIV-1 replication maintains the tissue reservoir during therapy journal January 2016
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
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
Prediction of HIV-1 and HIV-2 proteins by using Chou’s pseudo amino acid compositions and different classifiers journal February 2018
Estimating the mutational fitness effects distribution during early HIV infection journal July 2018
Impact of suboptimal APOBEC3G neutralization on the emergence of HIV drug resistance in humanized mice journal January 2019
Increasing the CpG dinucleotide abundance in the HIV-1 genomic RNA inhibits viral replication journal November 2017
Recent advances in understanding HIV evolution journal January 2017
Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation journal May 2016
Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region journal December 2017

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Related Subjects

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