Changes in the cellular proteins of A549 infected with Hepatitis E virus by proteomics analysis

Shen, Yin; Pu, Yingyan; Fu, Xingli; Xie, Ying; Bian, Xiaobo; Yang, Shixing; Yang, Yan; Cui, Li; Wang, Xiaochun; Wang, Hua; Zhang, Wen

doi:10.1186/s12917-014-0188-5

Cited by 12 publications

(9 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are consistent with the observations of this study, and previous studies demonstrated that the Mongolian gerbil represent a promising model for the studies on HEV infection and pathogenesis ( Doceul et al, 2016 ). In vitro , HEV cultivation was performed using PLC/PRF/5 and A549 using fecal suspension infected with HEV ( Tanaka et al, 2007 , 2009 ; Takahashi et al, 2010 ; Shen et al, 2014 ), and structural changes to the cells were investigated by TEM, showing that the lysosome numbers increased, indicating apoptosis, and cell membrane was damaged ( Shen et al, 2014 ), which was also consistent with our research.…”

Section: Discussionsupporting

confidence: 86%

Hepatitis E Virus Induces Hepatocyte Apoptosis via Mitochondrial Pathway in Mongolian Gerbils

et al. 2018

View full text Add to dashboard Cite

Previous studies demonstrated that Mongolian gerbils can be infected by hepatitis E virus (HEV), which induces the hepatic injury. Here, the mitochondria in hepatocytes from HEV-infected gerbils were considerably swollen, thin cristae. After HEV infection, the activity of superoxide dismutase significantly decreased (p < 0.01), while malondialdehyde concentrations significantly increased, compared with those in the control group (p < 0.01). Adenosine triphosphatase levels decreased significantly in the hepatocyte of the inoculated groups, compared with those in control group (p < 0.05) at days 21, 28, 42 post-inoculation (dpi) as well. Furthermore, the levels of ATP synthetase ATP5A1 significantly decreased during HEV infection, compared with those in the control group (p < 0.05). According to the TdT mediated dUTP nick end labeling (TUNEL) detection, TUNEL positive hepatocytes increased in the inoculated group, compared with that in the control group (p < 0.05). Up-regulation of the mitochondrion-mediated apoptosis regulating proteins, Bax and Bcl-2, in the HEV-infected gerbils (p < 0.05) was observed. However, cytochrome c levels in mitochondria decreased, while this molecule was detected in the cytoplasm of the infected animals, in contrast to that in the control group. Apaf-1, and active caspase-9 and -3 levels were shown to be significantly higher in the inoculated group compared with those in the control group (p < 0.05). Taken together, our results demonstrated that HEV infection induces hepatocyte injuries and activity of the mitochondrial apoptotic pathway, which trigger the hepatocyte apoptosis in Mongolian gerbils.

show abstract

Section: Discussionsupporting

confidence: 86%

Hepatitis E Virus Induces Hepatocyte Apoptosis via Mitochondrial Pathway in Mongolian Gerbils

et al. 2018

View full text Add to dashboard Cite

show abstract

“…A quantitative proteomics study by Rogée et al (2015) evaluating the alteration of host factors during HEV infection in swine revealed an upregulation of HNRNPK in infected livers (Rogée et al, 2015). In another study of modulation of host factors during HEV infection in A549 cells, a significant increase in the expression of HNRNPH was observed in response to virus infection (Shen et al, 2014). Our study is consistent with these findings as it underlines a putative role of hnRNP proteins in modulating HEV RNA transcription by binding at the promoter site and HEV polymerase.…”

Section: Resultsmentioning

confidence: 99%

Protein Interactions Network of Hepatitis E Virus RNA and Polymerase With Host Proteins

Kanade¹,

Pingale²,

Karpe³

2019

Front. Microbiol.

View full text Add to dashboard Cite

Host-pathogen interactions are crucial for the successful propagation of pathogens inside the host cell. Knowledge of interactions between host proteins and viral proteins or viral RNA may provide clues for developing novel antiviral strategies. Hepatitis E virus (HEV), a water-borne pathogen that causes acute hepatitis in humans, is responsible for epidemics in developing countries. HEV pathology and molecular biology have been poorly explored due to the lack of efficient culture systems. A contemporary approach, to better understand the viral infection cycle at the molecular level, is the use of system biology tools depicting virus-host interactions. To determine the host proteins which participate in the regulation of HEV replication, we indentified liver cell proteins interacting with HEV RNA at its putative promoter region and those interacting with HEV polymerase (RdRp) protein. We employed affinity chromatography followed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to identify the interacting host proteins. Protein-protein interaction networks (PPI) were plotted and analyzed using web-based tools. Topological analysis of the network revealed that the constructed network is potentially significant and relevant for viral replication. Gene ontology and pathway enrichment analysis revealed that HEV RNA promoter- and polymerase-interacting host proteins belong to different cellular pathways such as RNA splicing, RNA metabolism, protein processing in endoplasmic reticulum, unfolded protein response, innate immune pathways, secretory vesicle pathway, and glucose metabolism. We showed that hnRNPK and hnRNPA2B1 interact with both HEV putative promoters and HEV RdRp, which suggest that they may have crucial roles in HEV replication. We demonstrated in vitro binding of hnRNPK and hnRNPA2B1 proteins with the HEV targets in the study, assuring the authenticity of the interactions obtained through mass spectrometry. Thus, our study highlights the ability of viruses, such as HEV, to maneuver host systems to create favorable cellular environments for virus propagation. Studying the host-virus interactions can facilitate the identification of antiviral therapeutic strategies and novel targets.

show abstract

“…Differential protein profiles of expression that occurred during HEV infection have been reported for g-1, g-3, and g-4 viruses ( 24 – 26 ). Comparison of the H HEV data set with the g-1, g-3, and g-4 virus data sets revealed that 10/18 (g-1), 7/55 (g − 3), and 2/26 (g − 4) differentially expressed proteins also interact with a viral protein, which might account for their differential expression results ( Fig.…”

Section: Resultsmentioning

confidence: 90%

“…Yellow denotes the target of eIF2AK4. A Web-based tool, Venny 2.1.0 ( http://bioinfogp.cnb.csic.es/tools/venny/index.html ), was used to generate the Venn diagram for comparing the Y2H data set (this study) with the profiles of differentially expressed proteins identified in HEV-infected human, pigs, and A549 cells ( 24 – 26 ).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus

et al. 2018

View full text Add to dashboard Cite

Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.

show abstract

Changes in the cellular proteins of A549 infected with Hepatitis E virus by proteomics analysis

Cited by 12 publications

References 29 publications

Hepatitis E Virus Induces Hepatocyte Apoptosis via Mitochondrial Pathway in Mongolian Gerbils

Hepatitis E Virus Induces Hepatocyte Apoptosis via Mitochondrial Pathway in Mongolian Gerbils

Protein Interactions Network of Hepatitis E Virus RNA and Polymerase With Host Proteins

Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus

Contact Info

Product

Resources

About