Golgi protein 73 facilitates the interaction of hepatitis C virus NS5A with apolipoprotein E to promote viral particle secretion

Zhang, Xuewu; Wang, Tianci; Dai, Xuechen; Zhang, Yecheng; Jiang, Huiling; Zhang, Qi; Liu, Fang; Wu, Kailang; Zhou, Hongyao; Wu, Jianguo

doi:10.1016/j.bbrc.2016.09.152

Cited by 8 publications

(4 citation statements)

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“…We could not exclude the possibility that GP73 may have other strategies to facilitate HCV infection, such as promoting HCV particle assembly and secretion [24], or mediating MAVS-NS3/4A interaction on MAM. We also reported that GP73 mediates the interaction of ApoE and HCV NS5A to promote viral secretion [37]. Further studies are needed to clarify other functions of GP73 in HCV life cycle and HCV associated liver diseases.…”

Section: Discussionmentioning

confidence: 99%

GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation

et al. 2017

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Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients’ serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway. Detailed studies revealed that HCV infection activates MAVS that in turn recruits TRAF6 via TRAF-interacting-motifs (TIMs), and TRAF6 subsequently directly recruits GP73 to MAVS via coiled-coil domain. After binding with MAVS and TRAF6, GP73 promotes MAVS and TRAF6 degradation through proteasome-dependent pathway. Moreover, GP73 attenuates IFN-β promoter, IFN-stimulated response element (ISRE) and nuclear factor κB (NF-κB) promoter and down-regulates IFN-β, IFN-λ1, interleukin-6 (IL-6) and IFN-stimulated gene 56 (ISG56), leading to the repression of host innate immunity. Finally, knock-down of GP73 down-regulates HCV infection and replication in Huh7-MAVSR cells and primary human hepatocytes (PHHs), but such repression is rescued by GP73m4 (a mutant GP73 resists to GP73-shRNA#4) in Huh7-MAVSR cells, suggesting that GP73 facilitates HCV infection. Taken together, we demonstrated that GP73 acts as a negative regulator of innate immunity to facilitate HCV infection by interacting with MAVS/TRAF6 and promoting MAVS/TRAF6 degradation. This study provides new insights into the mechanism of HCV infection and pathogenesis, and suggests that GP73 is a new potential antiviral target in the prevention and treatment of HCV associated diseases.

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Section: Discussionmentioning

confidence: 99%

GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation

et al. 2017

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“…The role of HBV in promoting hepatocellular carcinoma development was studied and characterized by Prof. Wu too [ 16 , 17 ]. In studies of HCV, he revealed the functions of the HCV NS2 protein, NS3 protein, NS5A protein, and the envelope protein E2 in the pathogenesis of viral infection [ 18 , 19 , 20 , 21 , 22 , 23 ]. He studied the cross talk between HCV and human immunodeficiency virus 1 (HIV-1) and revealed that these two viruses could promote each other’s replication in different ways [ 24 , 25 , 26 ].…”

Section: Academic Achievementsmentioning

confidence: 99%

In Memory of the Virologist Jianguo Wu, 1957–2022

Yang,

Yue,

Pan

et al. 2023

Viruses

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“…American scholar Kladney et al performed subtractive hybridization in liver cDNA libraries of healthy individuals and patients with acute adult giant cell hepatitis in 2000 and found that the mRNA expression in patients with adult giant cell hepatitis was specifically increased . The mRNA encodes a protein GP73 containing 401 amino acids, and its relative molecular mass is 4.5 × 10 4 . However, due to acidic amino acid effect and glycosylation of GP73, denaturation of GP73 protein was affected, and electrophoretic migration rate was decreased.…”

Section: Basic Overview Of Gp73mentioning

confidence: 99%

“…[53][54][55][56][57][58][59][60][61][62][63] The mRNA encodes a protein GP73 containing 401 amino acids, and its relative molecular mass is 4.5 × 10 4 . [64][65][66][67][68][69][70][71] However, due to acidic amino acid effect and glycosylation of GP73, denaturation of GP73 protein was affected, and electrophoretic migration rate was decreased. The relative molecular mass of GP73 in the polyacrylamide gel electrophoresis was slightly larger, GP73 band abnormally migrated in the Western blot, and its relative molecular mass was 7.3 × 10 4 .…”

Section: The Discovery Of Gp73mentioning

confidence: 99%

Golgi protein 73 and its diagnostic value in liver diseases

et al. 2018

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Golgi protein 73 (GP73, also referred to as Golph 2) with 400 amino acids is a 73 kDa transmembrane glycoprotein typically found in the cis-Golg complex. It is primarily expressed in epithelial cells, which has been found upregulated in hepatocytes in patients suffering from both viral and non-viral liver diseases. GP73 has drawn increasing attention for its potential application in the diagnosis of liver diseases such as hepatitis, liver cirrhosis and liver cancer. Herein, we reviewed the discovery history of GP73 and summarized studies by many groups around the world, aiming at understanding its structure, expression, function, detection methods and the relationship between GP73 and liver diseases in various settings.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Golgi protein 73 facilitates the interaction of hepatitis C virus NS5A with apolipoprotein E to promote viral particle secretion

Cited by 8 publications

References 28 publications

GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation

GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation

In Memory of the Virologist Jianguo Wu, 1957–2022

Golgi protein 73 and its diagnostic value in liver diseases

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