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Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
Open accessAbstract
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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“However, cellular RNA polymerase II, along with various viral and host factors, also influences retroviral mutations, particularly in HIV-1 (O’Neil et al. 2002, Mangeat et al. 2003, Chiu and Greene 2006, Hughes 2015).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Mangeat et al. 2003
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Metadata
- Authors
- Mangeat, B., Turelli, P., Caron, G., Friedli, M., Perrin, L., & Trono, D.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Trono, Didier
- Venue
- Nature
- Published
- 2003-05-28
- Volume
- 424
- Issue
- 6944
- Pages
- 99-103
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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