Hepatitis B virus dampens autophagy maturation via negative regulation of Rab7 expression

Zhou, Tianyu; Jin, Min; Ding, Yongsen; Zhang, Yi; Sun, Ye; Huang, Shiqian; Xie, Qing; Xu, Congfeng; Cai, Wei

doi:10.5582/bst.2016.01049

Cited by 37 publications

(21 citation statements)

References 31 publications

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“…This result is in agreement with previous studies reporting that HBV replication induced an incomplete autophagy pathway in hepatic and hepatoma cells [ 30 – 32 ]. Therefore, our results confirm previous in vitro and in vivo studies, and show that genotype F, one of the less characterized HBV genotypes, behaves as the other genotypes in relation to its capacity to regulate autophagy.…”

Section: Discussionsupporting

confidence: 94%

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations

et al. 2018

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Hepatitis B virus (HBV) genotypes and mutants have been associated with differences in clinical and virological characteristics. Autophagy is a cellular process that degrades long-lived proteins and damaged organelles. Viruses have evolved mechanisms to alter this process to survive in host cells. In this work, we studied the modulation of autophagy by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. HBV subgenotypes F1b and F4 replication induced accumulation of autophagosomes in hepatoma cells. However, no autophagic protein degradation was observed, indicating a blockage of autophagic flux at later stages. This inhibition of autophagy flux might be due to an impairment of lysosomal acidification in hepatoma cells. Moreover, HBV-mediated autophagy modulation was independent of the viral subgenotypes and enhanced in viruses with BCP and preCore naturally occurring mutations. These results contribute to understand the mechanisms by which different HBV variants contribute to the pathogenesis of HBV infections. In addition, this study is the first to describe the role that two highly prevalent naturally occurring mutations exert on the modulation of HBV-induced autophagy.

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Section: Discussionsupporting

confidence: 94%

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations

et al. 2018

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“…Recent studies demonstrate that many RNA and DNA virus infections can induce unidentical autophagy responses. For example, hepatitis C virus (HCV), Sindbis virus, and bluetongue virus (BTV) can enhance autophagy flux (8,37,38), while hepatitis B virus (HBV), HIV, respiratory syndrome virus, and herpes simplex virus 1 (HSV-1) inhibit autophagy flux by either inhibiting autophagosome formation or blocking the fusion of autophagosome with lysosome (39)(40)(41)(42). Recently, a report even showed that different autophagy flux responses originated from different cells infected with the same strain of rabies virus (43).…”

Section: Discussionmentioning

confidence: 99%

Respiratory Syncytial Virus Replication Is Promoted by Autophagy-Mediated Inhibition of Apoptosis

Zeng

et al. 2018

J Virol

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Respiratory syncytial virus (RSV) is the main cause of acute lower respiratory tract infection (ALRI) in children worldwide. Virus-host interactions affect the progression and prognosis of the infection. Autophagy plays important roles in virus-host interactions. Respiratory epithelial cells serve as the front line of host defense during RSV infection, However, it is still unclear how they interact with RSV. In this study, we found that RSV induced autophagy that favored RSV replication and exacerbated lung pathology Mechanistically, RSV induced complete autophagy flux through reactive oxygen species (ROS) generation and activation of the AMP-activated protein kinase/mammalian target of rapamycin (AMPK-MTOR) signaling pathway in HEp-2 cells. Furthermore, we evaluated the functions of autophagy in RSV replication and found that RSV replication was increased in HEp-2 cells treated with rapamycin but decreased remarkably in cells treated with 3-methylademine (3-MA) or wortmannin. Knockdown key molecules in the autophagy pathway with short hairpinp RNA (shRNA) against autophagy-related gene 5 (), autophagy-related gene 7 (), or or treatment with ROS scavenger N-acetyl-l-cysteine (NAC) and AMPK inhibitor (compound C) suppressed RSV replication. 3-MA or sh significantly decreased cell viability and increased cell apoptosis at 48 hours postinfection (hpi). Blocking apoptosis with Z-VAD-FMK partially restored virus replication at 48 hpi. Those results provide strong evidence that autophagy may function as a proviral mechanism in a cell-intrinsic manner during RSV infection. An understanding of the mechanisms that respiratory syncytial virus utilizes to interact with respiratory epithelial cells is critical to the development of novel antiviral strategies. In this study, we found that RSV induces autophagy through a ROS-AMPK signaling axis, which in turn promotes viral infection. Autophagy favors RSV replication through blocking cell apoptosis at 48 hpi. Mechanistically, RSV induces mitophagy, which maintains mitochondrial homeostasis and therefore decreases cytochrome release and apoptosis induction. This study provides a novel insight into this virus-host interaction, which may help to exploit new antiviral treatments targeting autophagy processes.

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“…Cells and tissues were lysed with RIPA containing protease and phosphatase inhibitors (Roche), and proteins were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis after denaturation, as described. 13 Immunoblot analysis was performed by initial transfer of proteins onto polyvinylidenefluoride filters, using a Mini Trans-Blot (Bio-Rad) followed by a blocking step with 5% non-fat milk in TBST for 2 h at room temperature and incubated with primary antibodies overnight at 4°C. The primary antibodies involved were antihuman NMI (Abcam, ab183724) and anti-glyceraldehyde phosphate dehydrogenase (GAPDH) (Cell Signaling Technology, D16H11).…”

Section: Methodsmentioning

confidence: 99%

N‐myc and STAT interactor correlates with severity and prognosis in acute‐on‐chronic liver failure of hepatitis B virus

Xiong

Zhou

et al. 2019

J of Gastro and Hepatol

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Background and Aim Hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) is characterized by acute deterioration of chronic liver disease with excessive inflammation. N‐myc and STAT interactor (NMI), an inflammation‐mediated protein, involves in various inflammatory‐related diseases, but the role of NMI in development and prognosis in HBV‐ACLF remains to be elucidated. Methods Serum NMI from healthy controls (HCs, n = 20), chronic hepatitis B (CHB, n = 50) patients, and HBV‐ACLF patients (n = 50) was determined using ELISA. NMI from peripheral blood mononuclear cells and liver was confirmed using quantitative real‐time polymerase chain reaction, Western blot, and immunofluorescence. Results Serum NMI was increased 1.9‐fold or 2.2‐fold from HBV‐ACLF patients compared with that from HCs (P < 0.01) or CHB patients (P < 0.01). Consistently, NMI from peripheral blood mononuclear cells was upregulated significantly from HBV‐ACLF patients compared with that from HCs and CHB patients at mRNA and protein levels. Hepatic NMI from HBV‐ACLF patients was 2.8‐fold higher than that from HCs. Serum NMI was correlated with Model for End‐stage Liver Disease, Chronic Liver Failure Consortium ACLF score, and ACLF grades. In contrast, serum NMI was significantly decreased in HBV‐ACLF ameliorated patients during follow‐up, whereas serum NMI was sustained at high levels in non‐ameliorated patients. Elevated serum NMI (≥ 198.5 pg/mL) was correlated with poor survival rate of HBV‐ACLF patients. Using receiver operating characteristics curves, it was suggested that serum NMI was a potential biomarker in predicting 3‐month mortality of HBV‐ACLF patients. Conclusions Our study highlights the potential role of NMI in assessing the development and prognosis of HBV‐ACLF.

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Hepatitis B virus dampens autophagy maturation via negative regulation of Rab7 expression

Cited by 37 publications

References 31 publications

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations

Respiratory Syncytial Virus Replication Is Promoted by Autophagy-Mediated Inhibition of Apoptosis

N‐myc and STAT interactor correlates with severity and prognosis in acute‐on‐chronic liver failure of hepatitis B virus

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