Evidence map›Paper›PMID 25330146›Full record

ArticlePLoS pathogens2014

APOBEC3D and APOBEC3F potently promote HIV-1 diversification and evolution in humanized mouse model.

Kei Sato, Junko S Takeuchi, Naoko Misawa, Taisuke Izumi, Tomoko Kobayashi, Yuichi Kimura, Shingo Iwami, Akifumi Takaori-Kondo, Wei-Shau Hu, Kazuyuki Aihara and 4 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed.

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  11. Molecular Biology and Diversification of Human Retroviruses.Frontiers in virology (Lausanne, Switzerland) · 2022
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Kei SatoLaboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan.
Junko S TakeuchiLaboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan.
Naoko MisawaLaboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan.
Taisuke IzumiViral Mutation Section, HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland, United States of America.
Tomoko KobayashiLaboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan.
Yuichi KimuraLaboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan.
Shingo IwamiDepartment of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.
Akifumi Takaori-KondoDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
Wei-Shau HuViral Recombination Section, HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland, United States of America.
Kazuyuki AiharaInstitute of Industrial Science, The University of Tokyo, Meguro-ku, Tokyo, Japan; Graduate School of Information Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
Mamoru ItoCentral Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
Dong Sung AnDivision of Hematology and Oncology, University of California, Los Angeles, Los Angeles, California, United States of America; School of Nursing, University of California, Los Angeles, Los Angeles, California, United States of America; AIDS Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
Vinay K PathakViral Mutation Section, HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland, United States of America.
Yoshio KoyanagiLaboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan.

Funding

Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
Structure and Function of Vif and APOBEC3 (A3) ProteinsZIABC010595 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PATHAK, VINAY K. · 2009 to 2025
$14.8M
Understanding Retroviral Reverse Transcription, Recombination, and ReplicationZIABC010504 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HU, WEI-SHAU · 2009 to 2025
$5.3M
NIAID NIH HHS 5P30AI028697NIAID NIH HHS P30 AI028697
6 · The paper itself

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.

Indexed as

HIV-1AnimalsBiological EvolutionChromosome MappingCytidine DeaminaseCytosine DeaminaseDisease Models, AnimalGenetic VariationHumansMiceMutationReceptors, CXCR4RNA, ViralVirus ReplicationAPOBEC3D protein, humanAPOBEC3F protein, humanCytidine DeaminaseCytosine DeaminaseReceptors, CXCR4RNA, Viral

Identifiers

PMID25330146
PMCPMC4199767

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.