Evidence map›Paper›PMID 22828015›Full record

ArticleRetrovirology2012

Moloney murine leukemia virus glyco-gag facilitates xenotropic murine leukemia virus-related virus replication through human APOBEC3-independent mechanisms.

Takayuki Nitta, Sangouk Lee, Dat Ha, Maribel Arias, Christine A Kozak, Hung Fan

Open access · goldAbstract readComparative Study
In one paragraph

Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 22 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Takayuki NittaDepartment of Molecular Biology and Biochemistry and Cancer Research Institute, University of California, Irvine, CA 92697-3905, USA.
Sangouk Lee
Dat Ha
Maribel Arias
Christine A Kozak
Hung Fan
University of California, Irvine · USNational Institutes of Health · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Genetic Aspects Of Viral Oncogenesis In Wild Mouse SpeciesZIAAI000300 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KOZAK, CHRISTINE · 2009 to 2025
$19.0M
Oncogenesis By Jaagsiekte Sheep RetrovirusR01CA094188 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI FAN, HUNG Y. · 2002 to 2011
$3.2M
Intramural NIH HHSNCI NIH HHS CA94188NCI NIH HHS P30 CA062203
6 · The paper itself

Abstract

backgroundOne of the unique features of gammaretroviruses is that they contain an additional extended form of Gag, glyco-gag, which initiates in the leader sequence. MuLV glyco-gag, gPr80Gag, promotes retrovirus replication and disease progression. Although virtually all infectious MuLVs encode glyco-gag, XMRV (xenotropic murine leukemia virus-related virus) lacks the classical gPr80Gag sequence. We examined XMRV to determine if its leader sequence contains glyco-gag activity, whether the presence of conventional gPr80Gag affects replication of XMRV, and we describe the evolution of glyco-gag-deficient MuLVs in Mus.

resultsWe introduced several mutations disrupting two putative but noncanonical glyco-gag proteins in the leader sequence region in XMRV and found that those mutations did not affect virus release nor susceptibility to the antiviral activity of hA3G (human APOBEC3G). A chimeric XMRV encoding the Moloney MuLV (M-MuLV) leader sequence (MXMRV) demonstrated that M-MuLV glyco-gag facilitated MXMRV release and increased infectivity. Infectivity assays with several cell lines showed that glyco-gag increases XMRV infectivity in all cell lines tested, but the level of this increase varies in different cell lines. Because MuLV glyco-gag counteracts mouse APOBEC3, we investigated whether M-MuLV glyco-gag enhances XMRV infection by counteracting human APOBEC3. Comparison of hAPOBEC3 isoforms expressed in different cell lines indicated that hA3B was the most likely candidate for a restrictive hA3. However over-expression of hA3B showed no enhanced restriction of infection by XMRV compared to MXMRV. Endogenous MuLVs in the sequenced mouse genome were screened for canonical glyco-gag, which was identified in two clades of xenotropic MuLVs (X-MuLVs) and ecotropic MuLVs, but not in other X-MuLVs or in any polytropic MuLVs.

conclusionsM-MuLV glyco-gag facilitates XMRV replication, and the leader sequence region in XMRV does not encode proteins equivalent to M-MuLV glyco-gag. The fact that the ability of glyco-gag to enhance XMRV infection varies in different cell lines suggests a glyco-gag sensitive restrictive factor that further reduces XMRV infectivity. The M-MuLV glyco-gag enhancement for XMRV replication is through a hAPOBEC3 independent mechanism. The absence of glyco-gag in MuLVs carried by western European mice suggests that loss of this sequence is a relatively recent event with limited subspecies distribution.

Indexed as

Virus ReplicationAmino Acid SequenceAnimalsAPOBEC DeaminasesBase SequenceCytidine DeaminaseCytosine DeaminaseEvolution, MolecularGene Products, gagGenome, ViralGlycoproteinsGlycosylationHEK293 CellsHeLa CellsHep G2 CellsHumansAPOBEC3 proteins, humanAPOBEC DeaminasesCytidine DeaminaseCytosine DeaminaseGene Products, gagGlycoproteinsIsoenzymes

Identifiers

PMID22828015
PMCPMC3423011
OpenAlexW2099139016

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.