Cited by 1,486HIV Research and TreatmentRNA regulation and diseaseHIV/AIDS drug development and treatment

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Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts

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Mangeat, Bastien, Turelli, Priscilla, Caron, Gersende, Friedli, Marc, Perrin, Luc, Trono, Didier·2003·Nature

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Abstract

Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes. When produced in the presence of APOBEC3G, vif-defective virus is non-infectious. APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA. APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown. Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA. We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.

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Authors: Mangeat, B., Turelli, P., Caron, G., Friedli, M., Perrin, L., & Trono, D.
Affiliations: University of Geneva (CH)
Corresponding author: Trono, Didier
ORCID: Mangeat, Bastien
Turelli, Priscilla
Caron, Gersende
Trono, Didier
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2003-05-28
Volume: 424
Issue: 6944
Pages: 99-103
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature01709
OpenAlex: W1966343819
Cited by: 1,486
References: 28
Citations by year: 2026: 20 · 2025: 29 · 2024: 23 · 2023: 28 · 2022: 25 · 2021: 43 · 2020: 37 · 2019: 53 · 2018: 49 · 2017: 56 · 2016: 58 · 2015: 58 · 2014: 79 · 2013: 87 · 2012: 97
FWCI: 36.98
Type: journal article
Language: en
Open access: green
infoscience.epfl.ch
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords: APOBEC3G, HIV-1 Vif, APOBEC1, cytosine deamination, reverse transcription, G-to-A hypermutation, retrovirus restriction, T cells, RNA editing
MeSH terms: APOBEC-3G Deaminase, Antiviral Agents, Base Sequence, Cell Line, Cytidine Deaminase, DNA, Viral, Humans, Molecular Sequence Data, Nucleoside Deaminases, Proteins, Repressor Proteins, RNA, Messenger, Transcription, Genetic, Virus Replication, HIV-1, Mutagenesis, Gene Products, vif, Point Mutation, RNA Editing, Viral Load, vif Gene Products, Human Immunodeficiency Virus

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Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts

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