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

ABSTRACT Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepa...

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Autores principales:	Chandru Subramani, Vidya P. Nair, Saumya Anang, Sukhen Das Mandal, Madhu Pareek, Nidhi Kaushik, Akriti Srivastava, Sudipto Saha, Shalimar, Baibaswata Nayak, C. T. Ranjith-Kumar, Milan Surjit
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	hepatitis E virus host-pathogen interactions protein-protein interactions Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/839044181a1448c28a83c352cc9c342f
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spelling	oai:doaj.org-article:839044181a1448c28a83c352cc9c342f2021-12-02T19:45:30ZHost-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus10.1128/mSystems.00135-172379-5077https://doaj.org/article/839044181a1448c28a83c352cc9c342f2018-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00135-17https://doaj.org/toc/2379-5077ABSTRACT Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated 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 the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE 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.Chandru SubramaniVidya P. NairSaumya AnangSukhen Das MandalMadhu PareekNidhi KaushikAkriti SrivastavaSudipto SahaShalimarBaibaswata NayakC. T. Ranjith-KumarMilan SurjitAmerican Society for Microbiologyarticlehepatitis E virushost-pathogen interactionsprotein-protein interactionsMicrobiologyQR1-502ENmSystems, Vol 3, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatitis E virus host-pathogen interactions protein-protein interactions Microbiology QR1-502
spellingShingle	hepatitis E virus host-pathogen interactions protein-protein interactions Microbiology QR1-502 Chandru Subramani Vidya P. Nair Saumya Anang Sukhen Das Mandal Madhu Pareek Nidhi Kaushik Akriti Srivastava Sudipto Saha Shalimar Baibaswata Nayak C. T. Ranjith-Kumar Milan Surjit Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus
description	ABSTRACT Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated 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 the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE 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.
format	article
author	Chandru Subramani Vidya P. Nair Saumya Anang Sukhen Das Mandal Madhu Pareek Nidhi Kaushik Akriti Srivastava Sudipto Saha Shalimar Baibaswata Nayak C. T. Ranjith-Kumar Milan Surjit
author_facet	Chandru Subramani Vidya P. Nair Saumya Anang Sukhen Das Mandal Madhu Pareek Nidhi Kaushik Akriti Srivastava Sudipto Saha Shalimar Baibaswata Nayak C. T. Ranjith-Kumar Milan Surjit
author_sort	Chandru Subramani
title	Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus
title_short	Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus
title_full	Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus
title_fullStr	Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus
title_full_unstemmed	Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus
title_sort	host-virus protein interaction network reveals the involvement of multiple host processes in the life cycle of hepatitis e virus
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/839044181a1448c28a83c352cc9c342f
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Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus

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