Evidence map›Paper›PMID 36512270›Full record

ArticleInfection2023

Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication.

Yi-Jung Li, Jiun-Wen Wang, Hsin-Hsu Wu, Hsu-Han Wang, Yang-Jen Chiang, Huang-Yu Yang, Hsiang-Hao Hsu, Chih-Wei Yang, Ya-Chung Tian

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

Article in Infection, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 27% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
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

9 authors at 3 institutions in 1 country.

Yi-Jung LiKidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, No 5, Fusing St., Taoyuan, 333, Taiwan.
Jiun-Wen WangKidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, No 5, Fusing St., Taoyuan, 333, Taiwan.
Hsin-Hsu WuKidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, No 5, Fusing St., Taoyuan, 333, Taiwan.
Hsu-Han WangDepartment of Medicine, Chang Gung University, Taoyuan, Taiwan.
Yang-Jen ChiangDepartment of Medicine, Chang Gung University, Taoyuan, Taiwan.
Huang-Yu YangKidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, No 5, Fusing St., Taoyuan, 333, Taiwan.
Hsiang-Hao HsuKidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, No 5, Fusing St., Taoyuan, 333, Taiwan.
Chih-Wei YangKidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, No 5, Fusing St., Taoyuan, 333, Taiwan.
Ya-Chung TianKidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, No 5, Fusing St., Taoyuan, 333, Taiwan. dryctian@cgmh.org.tw.
Chang Gung University · TWChang Gung Memorial Hospital · TWLinkou Chang Gung Memorial Hospital · TW

Funding

Chung Gang Medical Research Project CMRPG3H0601Chung Gang Medical Research Project CMRPG3K0592National Science Council of Taiwan NRRPG3J6023
6 · The paper itself

Abstract

purposeBK Polyomavirus (BKPyV) infection manifests as renal inflammation and can cause kidney damage. Tumor necrosis factor-α (TNF-α) is increased in renal inflammation and injury. The aim of this study was to investigate the effect of TNF-α blockade on BKPyV infection.

methodsUrine specimens from 22 patients with BKPyV-associated nephropathy (BKPyVN) and 35 non-BKPyVN kidney transplant recipients were analyzed.

resultsWe demonstrated increased urinary levels of TNF-α and its receptors, TNFR1 and TNFR2, in BKPyVN patients. Treating BKPyV-infected human proximal tubular cells (HRPTECs) with TNF-α stimulated the expression of large T antigen and viral capsid protein-1 mRNA and proteins and BKPyV promoter activity. Knockdown of TNFR1 or TNFR2 expression caused a reduction in TNF-α-stimulated viral replication. NF-κB activation induced by overexpression of constitutively active IKK2 significantly increased viral replication and the activity of the BKPyV promoter containing an NF-κB binding site. The addition of a NF-κB inhibitor on BKPyV-infected cells suppressed viral replication. Blockade of TNF-α functionality by etanercept reduced BKPyV-stimulated expression of TNF-α, interleukin-1β (IL-1β), IL-6 and IL-8 and suppressed TNF-α-stimulated viral replication. In cultured HRPTECs and THP-1 cells, BKPyV infection led to increased expression of TNF-α, interleukin-1 β (IL-1β), IL-6 and TNFR1 and TNFR2 but the stimulated magnitude was far less than that induced by poly(I:C). This may suggest that BKPyV-mediated autocrine effect is not a major source of TNFα.

conclusionTNF-α stimulates BKPyV replication and inhibition of its signal cascade or functionality attenuates its stimulatory effect. Our study provides a therapeutic anti-BKPyV target.

Indexed as

BK VirusPolyomavirus InfectionsHumansInflammationInterleukin-6NF-kappa BReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaInterleukin-6NF-kappa BReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaBK polyomavirusBKPyV-associated nephropathyLarge T antigenNuclear factor-κBTumor necrosis factor-α

Identifiers

PMID36512270
PMCPMC9745287
OpenAlexW4312066105

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.