ArticlePLoS pathogens2014
APOBEC3D and APOBEC3F potently promote HIV-1 diversification and evolution in humanized mouse model.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential.Life science alliance · 2026Article
- APOBEC3 Proteins: From Antiviral Immunity to Oncogenic Drivers in HPV-Positive Cancers.Viruses · 2025Review
- APOBEC3-Related Editing and Non-Editing Determinants of HIV-1 and HTLV-1 Restriction.International journal of molecular sciences · 2025Review
- An in vitro cytidine deaminase assay to monitor APOBEC activity on DNA.Methods in enzymology · 2025Article
- Regulatory variants of APOBEC3 genes potentially associate with COVID-19 severity in populations with African ancestry.Scientific reports · 2023Article
- Article
- APOBEC3 degradation is the primary function of HIV-1 Vif for virus replication in the myeloid cell line THP-1.bioRxiv : the preprint server for biology · 2023Article
- Antiretroviral APOBEC3 cytidine deaminases alter HIV-1 provirus integration site profiles.Nature communications · 2023Article
- Antithetic effect of interferon-α on cell-free and cell-to-cell HIV-1 infection.PLoS computational biology · 2022Article
- Differential Activity of APOBEC3F, APOBEC3G, and APOBEC3H in the Restriction of HIV-2.Journal of molecular biology · 2022Article
- Molecular Biology and Diversification of Human Retroviruses.Frontiers in virology (Lausanne, Switzerland) · 2022Article
- A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor.Biomedicines · 2021Article
- IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells.iScience · 2021Article
- Human APOBEC3 Variations and Viral Infection.Viruses · 2021Review
- Comprehensive Investigation on the Interplay between Feline APOBEC3Z3 Proteins and Feline Immunodeficiency Virus Vif Proteins.Journal of virology · 2021Article
- Review
- A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans.PLoS pathogens · 2020Article
- Review
- Impact of Suboptimal APOBEC3G Neutralization on the Emergence of HIV Drug Resistance in Humanized Mice.Journal of virology · 2020Article
- An Alu Element Insertion in Intron 1 Results in Aberrant Alternative Splicing of APOBEC3G Pre-mRNA in Northern Pig-Tailed Macaques (Journal of virology · 2020Article
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Authors and funding
14 authors.
Funding
Abstract
Several APOBEC3 proteins, particularly APOBEC3D, APOBEC3F, and APOBEC3G, induce G-to-A hypermutations in HIV-1 genome, and abrogate viral replication in experimental systems, but their relative contributions to controlling viral replication and viral genetic variation in vivo have not been elucidated. On the other hand, an HIV-1-encoded protein, Vif, can degrade these APOBEC3 proteins via a ubiquitin/proteasome pathway. Although APOBEC3 proteins have been widely considered as potent restriction factors against HIV-1, it remains unclear which endogenous APOBEC3 protein(s) affect HIV-1 propagation in vivo. Here we use a humanized mouse model and HIV-1 with mutations in Vif motifs that are responsible for specific APOBEC3 interactions, DRMR/AAAA (4A) or YRHHY/AAAAA (5A), and demonstrate that endogenous APOBEC3D/F and APOBEC3G exert strong anti-HIV-1 activity in vivo. We also show that the growth kinetics of 4A HIV-1 negatively correlated with the expression level of APOBEC3F. Moreover, single genome sequencing analyses of viral RNA in plasma of infected mice reveal that 4A HIV-1 is specifically and significantly diversified. Furthermore, a mutated virus that is capable of using both CCR5 and CXCR4 as entry coreceptor is specifically detected in 4A HIV-1-infected mice. Taken together, our results demonstrate that APOBEC3D/F and APOBEC3G fundamentally work as restriction factors against HIV-1 in vivo, but at the same time, that APOBEC3D and APOBEC3F are capable of promoting viral diversification and evolution in vivo.
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