Desmethoxycurcumin aids IFNα's anti-HBV activity by antagonising CRYAB reduction and stabilising IFNAR1 protein
The eradication of chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection is a crucial goal in clinical practice. Enhancing the anti-HBV activity of interferon type I (IFNI) is a key strategy for achieving a functional cure for CHB. In this study, we investigated the effect of combined treatment with IFNα and Desmethoxycurcumin (DMC) on HBV replication in HepG2 cells and explored the underlying mechanism. Our results indicated IFNα alone was ineffective in completely inhibiting HBV replication, which was attributed to the virus-induced down-regulation of IFNI receptor 1 (IFNAR1) protein. However, the addition of a low dose of DMC significantly synergized with IFNα, leading to notable enhancement of IFNα anti-HBV activity. This effect was achieved by stabilising the IFNAR1 protein. Further investigation revealed that low dose DMC effectively blocked the ubiquitination-mediated degradation of IFNAR1, which was accomplished by rescuing the protein levels of alphaB-crystallin (CRYAB) and orchestrating the interaction between CRYAB and the E3 ubiquitin ligase, β-Trcp. Importantly, over-expression of CRYAB was found to favour the antiviral activity of IFNα against HBV replication. In conclusion, our study demonstrates that low-dose DMC enhanced the anti-HBV activity of IFNα by counteracting the reduction of CRYAB and stabilising the IFNAR1 protein.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
|---|---|
| Enthalten in: |
Journal of drug targeting - 31(2023), 9 vom: 01. Dez., Seite 976-985 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wei, Jinlai [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antagonize |
|---|
| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/1061186X.2023.2273200 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36343898X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36343898X | ||
| 003 | DE-627 | ||
| 005 | 20240214232845.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/1061186X.2023.2273200 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1292.xml |
| 035 | |a (DE-627)NLM36343898X | ||
| 035 | |a (NLM)37851377 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wei, Jinlai |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Desmethoxycurcumin aids IFNα's anti-HBV activity by antagonising CRYAB reduction and stabilising IFNAR1 protein |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The eradication of chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection is a crucial goal in clinical practice. Enhancing the anti-HBV activity of interferon type I (IFNI) is a key strategy for achieving a functional cure for CHB. In this study, we investigated the effect of combined treatment with IFNα and Desmethoxycurcumin (DMC) on HBV replication in HepG2 cells and explored the underlying mechanism. Our results indicated IFNα alone was ineffective in completely inhibiting HBV replication, which was attributed to the virus-induced down-regulation of IFNI receptor 1 (IFNAR1) protein. However, the addition of a low dose of DMC significantly synergized with IFNα, leading to notable enhancement of IFNα anti-HBV activity. This effect was achieved by stabilising the IFNAR1 protein. Further investigation revealed that low dose DMC effectively blocked the ubiquitination-mediated degradation of IFNAR1, which was accomplished by rescuing the protein levels of alphaB-crystallin (CRYAB) and orchestrating the interaction between CRYAB and the E3 ubiquitin ligase, β-Trcp. Importantly, over-expression of CRYAB was found to favour the antiviral activity of IFNα against HBV replication. In conclusion, our study demonstrates that low-dose DMC enhanced the anti-HBV activity of IFNα by counteracting the reduction of CRYAB and stabilising the IFNAR1 protein | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DMC | |
| 650 | 4 | |a HBV immune escape | |
| 650 | 4 | |a IFNAR1 degradation | |
| 650 | 4 | |a antagonize | |
| 650 | 4 | |a cRYAB | |
| 650 | 7 | |a Interferon-alpha |2 NLM | |
| 650 | 7 | |a desmethoxycurcumin |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Curcumin |2 NLM | |
| 650 | 7 | |a IT942ZTH98 |2 NLM | |
| 700 | 1 | |a Deng, Xichuan |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Wenying |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Lingxin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Guangyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Xinyue |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xinyue |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Zhixing |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Tingting |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of drug targeting |d 1996 |g 31(2023), 9 vom: 01. Dez., Seite 976-985 |w (DE-627)NLM074733958 |x 1029-2330 |7 nnns |
| 773 | 1 | 8 | |g volume:31 |g year:2023 |g number:9 |g day:01 |g month:12 |g pages:976-985 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/1061186X.2023.2273200 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 31 |j 2023 |e 9 |b 01 |c 12 |h 976-985 | ||