Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication.
Purpose: BK 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. Methods: Urine specimens fr...
| Publicado en: | Infection Vol. 51; no. 4; pp. 967 - 981 |
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| Autores principales: | , , , , , , , , |
| Formato: | clinical trial pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Aug2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=164982763&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 164982763 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03008126 NXO jtl: Infection issn: 03008126 maglogo: N pubinfo: dt: Aug2023 vid: 51 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 164982763 160756588 164982763 164982763 10.1007/s15010-022-01962-0 164982763 ppf: 967 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication. aug: au: Li, Yi-Jung Wang, Jiun-Wen Wu, Hsin-Hsu Wang, Hsu-Han Chiang, Yang-Jen Yang, Huang-Yu Hsu, Hsiang-Hao Yang, Chih-Wei Tian, Ya-Chung affil: Kidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, No 5, Fusing St., 333, Taoyuan, Taiwan sug: subj: Polyomavirus Infections Drug Therapy Tumor Necrosis Factor Inhibitors Pharmacodynamics Polyomaviridae Drug Effects Treatment Outcomes Human Funding Source Urinalysis NF-kappa B Interleukins Polyomavirus Infections Complications Kidney Diseases Risk Factors Risk Assessment Kidney Diseases Prevention and Control Gene Expression Clinical Trials ab: Purpose: BK 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. Methods: Urine specimens from 22 patients with BKPyV-associated nephropathy (BKPyVN) and 35 non-BKPyVN kidney transplant recipients were analyzed. Results: We 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. Conclusion: TNF-α stimulates BKPyV replication and inhibition of its signal cascade or functionality attenuates its stimulatory effect. Our study provides a therapeutic anti-BKPyV target. pubtype: Academic Journal doctype: clinical trial pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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