Antiviral Mechanism and Biochemical Basis of the Human APOBEC3 Family

The human APOBEC3 (A3) family (A, B, C, DE, F, G, and H) comprises host defense factors that potently inhibit the replication of diverse retroviruses, retrotransposons, and the other viral pathogens. HIV-1 has a counterstrategy that includes expressing the Vif protein to abrogate A3 antiviral function. Without Vif, A3 proteins, particularly APOBEC3G (A3G) and APOBEC3F (A3F), inhibit HIV-1 replication by blocking reverse transcription and/or integration and hypermutating nascent viral cDNA. The molecular mechanisms of this antiviral activity have been primarily attributed to two biochemical characteristics common to A3 proteins: catalyzing cytidine deamination in single-stranded DNA (ssDNA) and a nucleic acid-binding capability that is specific to ssDNA or ssRNA. Recent advances suggest that unique property of A3G dimer/oligomer formations, is also important for the modification of antiviral activity. In this review article we summarize how A3 proteins, particularly A3G, inhibit viral replication based on the biochemical and structural characteristics of the A3G protein.

• Publication year

  2012

• Venue

  Front. Microbio.

• Publication date

  2012-07-09

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fmicb.2012.00250PMID 22787460PMCID 3391693
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2012cited by this paper
• Endogenous APOBEC3B Restricts LINE-1 Retrotransposition in Transformed Cells and Human Embryonic Stem Cells*

  2011cited by this paper
• Deaminase Activity on Single-stranded DNA (ssDNA) Occurs in Vitro when APOBEC3G Cytidine Deaminase Forms Homotetramers and Higher-order Complexes*

  2011cited by this paper
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  2011cited by this paper
• Structural Features of Antiviral APOBEC3 Proteins are Linked to Their Functional Activities

  2011influential reference
• Structural Model for Deoxycytidine Deamination Mechanisms of the HIV-1 Inactivation Enzyme APOBEC3G*♦

  2010influential reference
• Atomic Force Microscopy Studies Provide Direct Evidence for Dimerization of the HIV Restriction Factor APOBEC3G

  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
• Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces.

  2010cited by this paper
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  2009cited by this paper
• Definition of the interacting interfaces of Apobec3G and HIV-1 Vif using MAPPIT mutagenesis analysis

  2009influential reference
• Restriction of HIV-1 by APOBEC3G is cytidine deaminase-dependent.

  2009cited by this paper
• A hydrodynamic analysis of APOBEC3G reveals a monomer-dimer-tetramer self-association that has implications for anti-HIV function.

  2009cited by this paper
• Deaminase-Independent Inhibition of Parvoviruses by the APOBEC3A Cytidine Deaminase

  2009cited by this paper
• Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA

  2009influential reference
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  2009cited by this paper
• APOBEC3G Subunits Self-associate via the C-terminal Deaminase Domain*

  2008cited by this paper
• A Model for Oligomeric Regulation of APOBEC3G Cytosine Deaminase-dependent Restriction of HIV*

  2008cited by this paper
• Function analysis of sequences in human APOBEC3G involved in Vif-mediated degradation.

  2008cited by this paper
• APOBEC3G-independent reduction in virion infectivity during long-term HIV-1 replication in terminally differentiated macrophages.

  2008cited by this paper
• Mouse APOBEC3 Restricts Friend Leukemia Virus Infection and Pathogenesis In Vivo

  2008cited by this paper
• Guidelines for Naming Nonprimate APOBEC3 Genes and Proteins

  2008cited by this paper
• Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications

  2008cited by this paper
• APOBEC3G Inhibits Elongation of HIV-1 Reverse Transcripts

  2008cited by this paper
• Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G

  2008cited by this paper
• Hepatitis B: modern concepts in pathogenesis – APOBEC3 cytidine deaminases as effectors in innate immunity against the hepatitis B virus

  2008cited by this paper
• APOBEC3G restricts early HIV-1 replication in the cytoplasm of target cells.

  2008cited by this paper
• Human APOBEC3G Can Restrict Retroviral Infection in Avian Cells and Acts Independently of both UNG and SMUG1

  2008cited by this paper
• Distinct Domains within APOBEC3G and APOBEC3F Interact with Separate Regions of Human Immunodeficiency Virus Type 1 Vif

  2008cited by this paper
• APOBEC3 inhibits mouse mammary tumour virus replication in vivo

  2007cited by this paper
• Population Level Analysis of Human Immunodeficiency Virus Type 1 Hypermutation and Its Relationship with APOBEC3G and vif Genetic Variation

  2007cited by this paper
• Cytidine Deaminases APOBEC3G and APOBEC3F Interact with Human Immunodeficiency Virus Type 1 Integrase and Inhibit Proviral DNA Formation

  2007influential reference
• Virion-associated Uracil DNA Glycosylase-2 and Apurinic/Apyrimidinic Endonuclease Are Involved in the Degradation of APOBEC3G-edited Nascent HIV-1 DNA*

  2007cited by this paper
• APOBEC3G Inhibits DNA Strand Transfer during HIV-1 Reverse Transcription*

  2007cited by this paper
• Human Immunodeficiency Virus Type 1 cDNAs Produced in the Presence of APOBEC3G Exhibit Defects in Plus-Strand DNA Transfer and Integration

  2007cited by this paper
• Deamination-Independent Inhibition of Hepatitis B Virus Reverse Transcription by APOBEC3G

  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
• Identification of Amino Acid Residues in APOBEC3G Required for Regulation by Human Immunodeficiency Virus Type 1 Vif and Virion Encapsidation

  2007influential reference
• Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G

  2007cited by this paper
• Effects of point mutations in the cytidine deaminase domains of APOBEC3B on replication and hypermutation of hepatitis B virus in vitro.

  2007cited by this paper
• Uracil DNA Glycosylase Is Dispensable for Human Immunodeficiency Virus Type 1 Replication and Does Not Contribute to the Antiviral Effects of the Cytidine Deaminase Apobec3G

  2006cited by this paper
• Biochemical Activities of Highly Purified, Catalytically Active Human APOBEC3G: Correlation with Antiviral Effect

  2006influential reference
• APOBEC3G DNA deaminase acts processively 3′ → 5′ on single-stranded DNA

  2006cited by this paper
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  2006cited by this paper
• Nanostructures of APOBEC3G Support a Hierarchical Assembly Model of High Molecular Mass Ribonucleoprotein Particles from Dimeric Subunits*

  2006cited by this paper
• Population Level Analysis of Human Immunodeficiency Virus Type 1 Hypermutation and Its Relationship with APOBEC3G and vif Genetic Variation

  2006cited by this paper
• Cellular inhibitors of long interspersed element 1 and Alu retrotransposition.

  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
• The Retroviral Hypermutation Specificity of APOBEC3F and APOBEC3G Is Governed by the C-terminal DNA Cytosine Deaminase Domain*

  2005cited by this paper
• Natural Variation in Vif: Differential Impact on APOBEC3G/3F and a Potential Role in HIV-1 Diversification

  2005cited by this paper
• Complementary function of the two catalytic domains of APOBEC3G.

  2005influential reference
• Nucleic acid chaperone activity of HIV-1 nucleocapsid protein: critical role in reverse transcription and molecular mechanism.

  2005cited by this paper
• A single amino acid substitution in human APOBEC3G antiretroviral enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion.

  2004influential reference
• Inhibition of Hepatitis B Virus Replication by APOBEC3G

  2004cited by this paper
• Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome

  2004influential reference
• APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase.

  2004cited by this paper
• A single amino acid difference in the host APOBEC3G protein controls the primate species specificity of HIV type 1 virion infectivity factor.

  2004cited by this paper
• Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo.

  2004cited by this paper
• A Single Amino Acid Determinant Governs the Species-specific Sensitivity of APOBEC3G to Vif Action*

  2004influential reference
• Human Apolipoprotein B mRNA-editing Enzyme-catalytic Polypeptide-like 3G (APOBEC3G) Is Incorporated into HIV-1 Virions through Interactions with Viral and Nonviral RNAs*

  2004cited by this paper
• A single amino acid of APOBEC3G controls its species-specific interaction with virion infectivity factor (Vif).

  2004cited by this paper
• HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation

  2003cited by this paper
• HIV-1 Vif: counteracting innate antiretroviral defenses.

  2003cited by this paper
• Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-SCF Complex

  2003cited by this paper
• Hypermutation of HIV-1 DNA in the Absence of the Vif Protein

  2003cited by this paper
• Death by deamination: a novel host restriction system for HIV-1.

  2003cited by this paper
• The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif

  2003cited by this paper
• Virology. Weapons of mutational destruction.

  2003cited by this paper
• Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business.

  2003cited by this paper
• DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses

  2003influential reference
• HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability.

  2003cited by this paper
• Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts

  2003influential reference
• Weapons of Mutational Destruction

  2003cited by this paper
• The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA

  2003influential reference
• Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif.

  2003cited by this paper
• DNA deamination mediates innate immunity to retroviral infection.

  2003cited by this paper
• Faculty Opinions recommendation of Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein.

  2002cited by this paper
• Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein

  2002cited by this paper
• An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22.

  2002cited by this paper
• Affinities of packaging domain loops in HIV-1 RNA for the nucleocapsid protein.

  2002cited by this paper
• An AU-Rich Sequence Element (UUUN[A/U]U) Downstream of the Edited C in Apolipoprotein B mRNA Is a High-Affinity Binding Site for Apobec-1: Binding of Apobec-1 to This Motif in the 3′ Untranslated Region of c-myc Increases mRNA Stability

  2000cited by this paper
• Human immunodeficiency virus type 1 Vif does not influence expression or virion incorporation of gag-, pol-, and env-encoded proteins

  1996influential reference
• Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site.

  1995cited by this paper
• apobec-1, the Catalytic Subunit of the Mammalian Apolipoprotein B mRNA Editing Enzyme, Is a Novel RNA-binding Protein (*)

  1995cited by this paper
• Efficiency of viral DNA synthesis during infection of permissive and nonpermissive cells with vif-negative human immunodeficiency virus type 1

  1993influential reference
• Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells

  1993influential reference
• The sor gene of HIV-1 is required for efficient virus transmission in vitro.

  1987influential reference
• The HIV A (sor) gene product is essential for virus infectivity

  1987influential reference
• Virology

  1955cited by this paper

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  2024cites this paper
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  2024cites this paper
• The Drivers, Mechanisms, and Consequences of Genome Instability in HPV-Driven Cancers

  2022cites this paper
• Retasking of canonical antiviral factors into proviral effectors.

  2022cites this paper
• Viruses with U-DNA: New Avenues for Biotechnology

  2021cites this paper
• APOBEC3G rescues cells from the deleterious effects of DNA damage

  2021cites this paper
• The Essential Co-Option of Uracil-DNA Glycosylases by Herpesviruses Invites Novel Antiviral Design

  2020cites this paper
• Targeting uracil-DNA glycosylases for therapeutic outcomes using insights from virus evolution.

  2019cites this paper
• APOBEC3G Regulation of the Evolutionary Race Between Adaptive Immunity and Viral Immune Escape Is Deeply Imprinted in the HIV Genome

  2019cites this paper
• Jembrana disease virus Vif antagonizes the inhibition of bovine APOBEC3 proteins through ubiquitin-mediate protein degradation.

  2018cites this paper
• Molecular Interactions of a DNA Modifying Enzyme APOBEC3F Catalytic Domain with a Single-Stranded DNA.

  2018cites this paper
• Genome polarity of RNA viruses reflects the different evolutionary pressures shaping codon usage

  2018cites this paper
• Enterovirus 71 antagonizes the inhibition of the host intrinsic antiviral factor A3G

  2018cites this paper
• Codon usage of HIV regulatory genes is not determined by nucleotide composition

  2017cites this paper
• Molecular Interactions of APOBEC3F Catalytic Domain with a Single-Stranded DNA.

  2017cites this paper
• Nanoscale Characterization of Interaction of APOBEC3G with RNA.

  2017cites this paper
• STUDIES ON THE MECHANISMS OF ANTI-HIV-1 FUNCTIONS OF APOBEC3F AND APOBEC3G

  2017cites this paper
• Inhibition of APOBEC3G activity impedes double‐stranded DNA repair

  2016cites this paper
• Zinc-mediated binding of a low-molecular-weight stabilizer of the host anti-viral factor apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G.

  2016cites this paper
• Nuclear Magnetic Resonance Structure of the APOBEC3B Catalytic Domain: Structural Basis for Substrate Binding and DNA Deaminase Activity.

  2016cites this paper
• The potential role of retroviruses in autoimmunity

  2016cites this paper
• APOBEC3G Interacts with ssDNA by Two Modes: AFM Studies

  2015cites this paper
• Characteristics of biological processes influenced by gut bacteria

  2015cites this paper
• Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities

  2015cites this paper
• Endogenous CCL2 neutralization restricts HIV-1 replication in primary human macrophages by inhibiting viral DNA accumulation

  2015cites this paper
• APOBECs and virus restriction.

  2015cites this paper
• Erratum to: Endogenous CCL2 neutralization restricts HIV-1 replication in primary human macrophages by inhibiting viral DNA accumulation

  2015cites this paper
• Human APOBEC3F incorporation into human immunodeficiency virus type 1 particles.

  2014cites this paper
• APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

  2014cites this paper
• Interaction of APOBEC3A with DNA Assessed by Atomic Force Microscopy

  2014cites this paper
• Biosafety Features of Lentiviral Vectors

  2013cites this paper
• Insight into the HIV-1 Vif SOCS-box–ElonginBC interaction

  2013cites this paper
• Manipulation of Cellular Processing Bodies and Their Constituents by Viruses

  2013cites this paper
• Restriction Genes for Retroviruses Influence the Risk of Multiple Sclerosis

  2013cites this paper
• Retroviruses, retroelements and their restrictions

  2013cites this paper
• Atomic force microscopy studies of APOBEC3G oligomerization and dynamics.

  2013cites this paper