Evidence map›Paper›PMID 15708995›Full record

ArticleJournal of virology2005

Human cytomegalovirus protein US11 provokes an unfolded protein response that may facilitate the degradation of class I major histocompatibility complex products.

Boaz Tirosh, Neal N Iwakoshi, Brendan N Lilley, Ann-Hwee Lee, Laurie H Glimcher, Hidde L Ploegh

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

42 citing papers in PubMed, 74 citations in OpenAlex.

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  17. ER stress-induced cell death mechanisms.Biochimica et biophysica acta · 2013
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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 1 institution in 1 country.

Boaz TiroshDepartment of Pathology, Harvard Medical School, 77 Ave. Louis Pasteur, Room 836, Boston MA 02115, USA.
Neal N Iwakoshi
Brendan N Lilley
Ann-Hwee Lee
Laurie H Glimcher
Hidde L Ploegh
Harvard University · US

Funding

Trageting the Multiple Myeloma EpigenomeP50CA100707 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MUNSHI, NIKHIL C. · 2003 to 2023
$45.0M
TRANSCRIPTIONAL REGULATION OF THE IMMUNE RESPONSER01AI032412 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI GLIMCHER, LAURIE HOLLIS · 1991 to 2010
$4.6M
ASSEMBLY OF MHC CLASS I MOLECULES IN VITRO AND IN VIVOR37AI033456 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI PLOEGH, HIDDE L · 1998 to 2007
$4.6M
NCI NIH HHS 1P50CA100707NCI NIH HHS P50 CA100707NIAID NIH HHS 5R37-AI33456NIAID NIH HHS AI32412NIAID NIH HHS R01 AI032412NIAID NIH HHS R37 AI033456
6 · The paper itself

Abstract

The human cytomegalovirus (HCMV) glycoprotein US11 diverts class I major histocompatibility complex (MHC) heavy chains (HC) from the endoplasmic reticulum (ER) to the cytosol, where HC are subjected to proteasome-mediated degradation. In mouse embryonic fibroblasts that are deficient for X-box binding protein 1 (XBP-1), a key transcription factor in the unfolded protein response (UPR) pathway, we show that degradation of endogenous mouse HC is impaired. Moreover, the rate of US11-mediated degradation of ectopically expressed HLA-A2 is reduced when XBP-1 is absent. In the human astrocytoma cell line U373, turning on expression of US11, but not US2, is sufficient to induce a UPR, as manifested by upregulation of the ER chaperone Bip and by splicing of XBP-1 mRNA. In the presence of dominant-negative versions of XBP-1 and activating transcription factor 6, the kinetics of class I MHC HC degradation were delayed when expression of US11 was turned on. The magnitude of these effects, while reproducible, was modest. Conversely, in cells that stably express high levels of US11, the degradation of HC is not affected by the presence of the dominant negative effectors of the UPR. An infection of human foreskin fibroblasts with human cytomegalovirus induced XBP-1 splicing in a manner that coincides with US11 expression. We conclude that the contribution of the UPR is more pronounced on HC degradation shortly after induction of US11 expression and that US11 is sufficient to induce such a response.

Indexed as

AnimalsCell LineCells, CulturedCytomegalovirusDNA-Binding ProteinsEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHistocompatibility Antigens Class IHumansMembrane GlycoproteinsMiceMice, KnockoutMolecular ChaperonesNuclear ProteinsProtein DenaturationRegulatory Factor X Transcription FactorsDNA-Binding ProteinsEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHistocompatibility Antigens Class IMembrane GlycoproteinsMolecular ChaperonesNuclear ProteinsRegulatory Factor X Transcription FactorsRNA-Binding ProteinsTranscription FactorsUS11 protein, herpesvirusUS2 protein, VaricellovirusViral Envelope ProteinsViral ProteinsX-Box Binding Protein 1XBP1 protein, humanXbp1 protein, mouse

Identifiers

PMID15708995
PMCPMC548438
OpenAlexW2170432403

What OpenQuestion holds

Textmetadata
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.