Hepatitis E virus ORF1 encoded non structural protein–host protein interaction network

Ojha, Nishant Kumar; Lole, Kavita S.

doi:10.1016/j.virusres.2015.12.007

Cited by 15 publications

(12 citation statements)

References 57 publications

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“…In summary, the data obtained in our study are likely to be of very high confidence for further analyses as they were selected through rigorous scrutiny. Though the interaction partners of some HEV proteins have been reported previously ( 22 , 41 ), this is the first report of identification of the host interactome of all HEV proteins. Further, inclusion of a brain library in the screening identified several new interaction partners which were not obtained in the earlier studies, as they screened only the liver library.…”

Section: Discussionmentioning

confidence: 76%

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

et al. 2018

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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.

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Section: Discussionmentioning

confidence: 76%

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

et al. 2018

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“…For a long time, HEV remained the understudied virus due to the lack of efficient culture system and the unavailability of specific antibodies against viral proteins. Recently, using Y2H screening of human liver cDNA library, we identified 44 cellular proteins interacting with HEV-macro domain [27]. Among total interacting cDNA clones, human FTL clones were abundant (30 % of the interacting cDNA clones).…”

Section: Discussionmentioning

confidence: 99%

“…To confirm observations of HEV-macro domain-human FTL binary interactions from our previous Y2H experiments that were carried out using human liver cell cDNA library [27], we repeated Y2H experiment using individual clones. For that, yeast strains Y187 and AH109 were transformed with pGADT7-FTL (AD) and pGBKT7-HEVmacro (BD) encoding plasmids, respectively and hybridized ( Fig.…”

Section: Hev-macro Domain Interacts With Ferritin Light Chain (Ftl)mentioning

confidence: 92%

“…Protocols for the yeast cell transformation, mating, and liquid b-galactosidase assay were carried out as per manufacturer's instructions. Yeast strain AH109 transformed with pGBKT7-macro was used as ''Bait'' has been described previously [27]. PCR product encoding human Ferritin Light Chain (FTL) gene, generated from our previous study was cloned into pGADT7 vector and yeast cells (strain Y187) were transformed with this plasmid and used as ''Prey''.…”

Section: Methodsmentioning

confidence: 99%

“…We have recently shown that protease, macro, and helicase domains of HEV pORF1 directly interact with light chain subunit of ferritin (FTL) using yeast two-hybrid system [27]. In the present study, we have analyzed the significance of FTL-macro domain interaction and its possible role during HEV pathogenesis.…”

Section: Introductionmentioning

confidence: 97%

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Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion

Ojha

Lole

2016

Mol Cell Biochem

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Hepatitis E Virus (HEV) is the major causative agent of acute hepatitis in developing countries. Its genome has three open reading frames (ORFs)-called as ORF1, ORF2, and ORF3. ORF1 encodes nonstructural polyprotein having multiple domains, namely: Methyltransferase, Y domain, Protease, Macro domain, Helicase, and RNA-dependent RNA polymerase. In the present study, we show that HEV-macro domain specifically interacts with light chain subunit of human ferritin (FTL). In cultured hepatoma cells, HEV-macro domain reduces secretion of ferritin without causing any change in the expression levels of FTL. This inhibitory effect was further enhanced upon Brefeldin-A treatment. The levels of transferrin Receptor 1 or ferroportin, two important proteins in iron metabolism, remained unchanged in HEV-macro domain expressing cells. Similarly, there were no alterations in the levels of cellular labile iron pool and reactive oxygen species, indicating that HEV-macro domain does not influence cellular iron homeostasis/metabolism. As ferritin is an acute-phase protein, secreted in higher level in infected persons and HEV-macro domain has the property of reducing synthesis of inflammatory cytokines, we propose that by directly binding to FTL, macro domain prevents ferritin from entering into circulation and helps in further attenuation of the host immune response.

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1H, 13C, 15N backbone resonance assignment of apo and ADP-ribose bound forms of the macro domain of Hepatitis E virus through solution NMR spectroscopy

et al. 2022

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The genome of Hepatitis E virus (HEV) is 7.2 kilobases long and has three open reading frames. The largest one is ORF1, encoding a non-structural protein involved in the replication process, and whose processing is ill-defined. The ORF1 protein is a multi-modular protein which includes a macro domain (MD). MDs are evolutionarily conserved structures throughout all kingdoms of life. MDs participate in the recognition and removal of ADP-ribosylation, and specifically viral MDs have been identified as erasers of ADP-ribose moieties interpreting them as important players at escaping the early stages of host-immune response. A detailed structural analysis of the apo and bound to ADP-ribose state of the native HEV MD would provide the structural information to understand how HEV MD is implicated in virus-host interplay and how it interacts with its intracellular partner during viral replication. In the present study we present the high yield expression of the native macro domain of HEV and its analysis by solution NMR spectroscopy. The HEV MD is folded in solution and we present a nearly complete backbone and sidechains assignment for apo and bound states. In addition, a secondary structure prediction by TALOS + analysis was performed. The results indicated that HEV MD has a α/β/α topology very similar to that of most viral macro domains.

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Hepatitis E virus ORF1 encoded non structural protein–host protein interaction network

Cited by 15 publications

References 57 publications

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

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

Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion

1H, 13C, 15N backbone resonance assignment of apo and ADP-ribose bound forms of the macro domain of Hepatitis E virus through solution NMR spectroscopy

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