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

Subramani, Chandru; Nair, Vidya Padmanabhan; Anang, Saumya; Mandal, Sukhen Das; Pareek, Madhu; Kaushik, Nidhi; Srivastav, Ajeet K.; Saha, Sudipto; Shalimar, S.; Nayak, Baibaswata; Ranjith-Kumar, C. T.; Surjit, Milan

doi:10.1128/msystems.00135-17

Cited by 45 publications

(37 citation statements)

References 61 publications

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“…The PDZ domain is a proteinprotein recognition sequence found in cellular adaptor proteins that coordinate host cell signalling pathways by binding to other proteins that have a complementary PBM. A number of these signalling pathways and processes are exploited by viruses for replication, propagation, and pathogenesis [153][154][155][156][157]. The PBM of SARS-CoV E is found in the last four amino acids (DLLV) of its C-terminus [1,82].…”

Section: Protein-protein Interactions: Host-viralmentioning

confidence: 99%

Coronavirus envelope protein: current knowledge

Schoeman

Fielding

2019

Virol J

1,817

1,859

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Background Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins. Main body This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research. Conclusions The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.

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Section: Protein-protein Interactions: Host-viralmentioning

confidence: 99%

Coronavirus envelope protein: current knowledge

Schoeman

Fielding

2019

Virol J

1,817

1,859

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“…Studies on several viruses reveal that viral proteins or viral RNA interact with host proteins to regulate viral replication. Previous studies on the HEV ORF1 and ORF2 interactome showed the involvement of factors associated with different biological processes, such as ubiquitin proteasome system, innate immunity and RNA metabolism (Ojha and Lole, 2016; Subramani et al, 2018). In another study by Paingankar et al host factors have been found to interact with the untranslated region on HEV genomic RNA (Paingankar and Arankalle, 2015).…”

Section: Introductionmentioning

confidence: 99%

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

Kanade¹,

Pingale²,

Karpe³

2019

Front. Microbiol.

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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.

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“…A yeast two-hybrid screen identified 138 protein–protein interactions between HEV and host proteins, indicating roles for HEV proteins in modulating host cell processes such as stress and immune responses, the ubiquitin–proteasome system, energy and iron metabolism, and protein translation. Most importantly, a set of host translation factors (eIF4A, eIF3A, and RACK1), required for HEV replication, was identified [ 39 ] ( Figure 1 and Table 1 ). As part of the eIF4F complex, eIF4A drives cap-dependent translation initiation in eukaryotes and has been involved in the replication of various RNA viruses.…”

Section: Who Wants To Play? – Interplay Between Host Cell and Viral Fmentioning

confidence: 99%

Virus–Host Cell Interplay during Hepatitis E Virus Infection

Wissing

Brüggemann

Steinmann

et al. 2021

Trends in Microbiology

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The molecular interplay between cellular host factors and viral proteins is a continuous process throughout the viral life cycle determining virus host range and pathogenesis. The hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans worldwide. However, the mechanisms of liver pathology and clinical disease remain poorly understood for HEV infection. This review summarizes our current understanding of HEV–host cell interactions and highlights experimental strategies and techniques to identify novel host components required for the viral life cycle as well as restriction factors. Understanding these interactions will provide insight into the viral life cycle of HEV and might further help to devise novel therapeutic strategies and antiviral targets.

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

Cited by 45 publications

References 61 publications

Coronavirus envelope protein: current knowledge

Coronavirus envelope protein: current knowledge

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

Virus–Host Cell Interplay during Hepatitis E Virus Infection

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