Evidence map›Paper›PMID 30297863›Full record

ArticleNature communications2018

Genetic and mechanistic basis for APOBEC3H alternative splicing, retrovirus restriction, and counteraction by HIV-1 protease.

Diako Ebrahimi, Christopher M Richards, Michael A Carpenter, Jiayi Wang, Terumasa Ikeda, Jordan T Becker, Adam Z Cheng, Jennifer L McCann, Nadine M Shaban, Daniel J Salamango and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
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

26 citing papers in PubMed, 33 citations in OpenAlex.

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  14. Endogenous APOBEC3B overexpression characterizes HPV-positive and HPV-negative oral epithelial dysplasias and head and neck cancers.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021
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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

15 authors at 3 institutions in 1 country.

Diako EbrahimiDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.ORCID http://orcid.org/0000-0002-8577-0420
Christopher M RichardsDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Michael A CarpenterDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Jiayi WangDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Terumasa IkedaDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Jordan T BeckerDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Adam Z ChengDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Jennifer L McCannDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Nadine M ShabanDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Daniel J SalamangoDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Gabriel J StarrettDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Jairam R LingappaDepartments of Global Health, Medicine and Pediatrics, University of Washington, Seattle, WA, 98104, USA.
Jeongsik YongDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
William L BrownDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Reuben S HarrisDepartment of Biochemistry, Molecular Biology and Biophysics, Masonic Cancer Center, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA. rsh@umn.edu.
University of Minnesota · USNational Institutes of Health · USUniversity of Washington · US

Funding

X-ray Crystallographic Fragment Screening CoreU54AI150472 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI LYUMKIS, DMITRY · 2019 to 2021
$15.7M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008244 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SHIMIZU, YOJI · 1988 to 2024
$13.6M
X-ray Crystallographic Fragment Screening CoreU54GM103368 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI SARAFIANOS, STEFAN G, TORBETT, BRUCE EDWARD · 2017 to 2018
$11.1M
Minnesota Craniofacial Research Training ProgramT90DE022732 · NIDCR · UNIVERSITY OF MINNESOTA · PI MANSKY, KIM CARPENTER · 2012 to 2023
$4.9M
APOBEC3 Proteins in HIV RestrictionR37AI064046 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HARRIS, REUBEN S · 2015 to 2024
$4.2M
Minnesota Training Program in VirologyT32AI083196 · NIAID · UNIVERSITY OF MINNESOTA · PI Louis M Mansky · 2010 to 2026
$3.2M
The Role of Truncated mRNAs in CancerR01GM113952 · NIGMS · UNIVERSITY OF MINNESOTA · PI YONG, JEONGSIK · 2015 to 2023
$3.0M
Molecular Determinants of HIV hypermutationR21AI138793 · NIAID · UNIVERSITY OF MINNESOTA · PI EBRAHIMI, DIAKO · 2018 to 2019
$470k
(PQ2) HIV INFECTION, APOBEC UPREGULATION, AND CANCER MUTAGENESISR21CA206309 · NCI · UNIVERSITY OF MINNESOTA · PI HARRIS, REUBEN S · 2016 to 2017
$401k
HIV-1 Vif in AIDS-Related MalignanciesF30CA200432 · NCI · UNIVERSITY OF MINNESOTA · PI CHENG, ADAM Z · 2015 to 2019
$213k
NCI NIH HHS F30 CA200432NCI NIH HHS R21 CA206309NIAID NIH HHS R21 AI138793NIAID NIH HHS R37 AI064046NIAID NIH HHS T32 AI083196NIDCR NIH HHS T90 DE022732NIGMS NIH HHS R01 GM113952NIGMS NIH HHS T32 GM008244NIGMS NIH HHS U54 GM103368
6 · The paper itself

Abstract

Human APOBEC3H (A3H) is a single-stranded DNA cytosine deaminase that inhibits HIV-1. Seven haplotypes (I-VII) and four splice variants (SV154/182/183/200) with differing antiviral activities and geographic distributions have been described, but the genetic and mechanistic basis for variant expression and function remains unclear. Using a combined bioinformatic/experimental analysis, we find that SV200 expression is specific to haplotype II, which is primarily found in sub-Saharan Africa. The underlying genetic mechanism for differential mRNA splicing is an ancient intronic deletion [del(ctc)] within A3H haplotype II sequence. We show that SV200 is at least fourfold more HIV-1 restrictive than other A3H splice variants. To counteract this elevated antiviral activity, HIV-1 protease cleaves SV200 into a shorter, less restrictive isoform. Our analyses indicate that, in addition to Vif-mediated degradation, HIV-1 may use protease as a  counter-defense mechanism against A3H in >80% of sub-Saharan African populations.

Indexed as

Alternative SplicingAmino Acid SequenceAminohydrolasesBase SequenceHaplotypesHEK293 CellsHIV-1HIV ProteaseHumansIsoenzymesPolymorphism, Single NucleotideSequence Homology, Amino AcidSequence Homology, Nucleic Acidvif Gene Products, Human Immunodeficiency VirusVirus ReplicationAminohydrolasesAPOBEC3H protein, humanHIV ProteaseIsoenzymesp16 protease, Human immunodeficiency virus 1vif Gene Products, Human Immunodeficiency Virusvif protein, Human immunodeficiency virus 1

Identifiers

PMID30297863
PMCPMC6175962
OpenAlexW2895591204

What OpenQuestion holds

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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.