Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection

Zika virus (ZIKV) is a member of the Flaviviridae family and was until recently a relatively obscure tropical disease. Subsequently, ZIKV has been shown to be the causative agent of fetal abnormalities and Guillain-Barré syndrome in outbreaks across the Americas and so efforts towards delineating im...

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Autores Principales: Royle, Jamie, Ramírez-Santana, Carolina, Akpunarlieva, Snezhana, Donald, Claire L, Gestuveo, Rommel J, Anaya, Juan-Manuel
Formato: Artículo (Article)
Lenguaje:Inglés (English)
Publicado: Microbiology Society 2019
Materias:
Acceso en línea:https://repository.urosario.edu.co/handle/10336/27782
https://doi.org/10.1099/acmi.imav2019.po0021
id ir-10336-27782
recordtype dspace
spelling ir-10336-277822021-08-12T02:45:31Z Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection La proteína 78 regulada por glucosa (GRP78) interactúa con la envoltura del virus del Zika y es necesaria para una infección productiva Royle, Jamie Ramírez-Santana, Carolina Akpunarlieva, Snezhana Donald, Claire L Gestuveo, Rommel J Anaya, Juan-Manuel Zika virus ZIKV infection Guillain-Barré syndrome GRP78 Proteomics Virus–cell interactions Zika virus (ZIKV) is a member of the Flaviviridae family and was until recently a relatively obscure tropical disease. Subsequently, ZIKV has been shown to be the causative agent of fetal abnormalities and Guillain-Barré syndrome in outbreaks across the Americas and so efforts towards delineating important factors in the viral lifecycle have increased. Combining protein pull-down with mass spectrometry, it was found that ZIKV envelope (Env) interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78) in A549 cells. Flaviviruses such as Japanese encephalitis virus and dengue virus are known to co-opt ER resident proteins and members of the unfolded protein response, including GRP78, to enhance viral infectivity and propagation. The role these proteins play during the ZIKV lifecycle has yet to be elucidated. To determine the importance of this interaction during ZIKV infection, A549 cells were treated with GRP78-specific siRNAs prior to infection with a NanoLuc expressing reporter virus or a wild-type virus. Depletion of GRP78 significantly reduced both virus luciferase readings and viral titres, indicating that GRP78 is necessary for efficient infection of mammalian cell culture. In contrast, inhibition of GRP78 with small molecule inhibitors did not reduce ZIKV infection. Interestingly, immunofluorescence of ZIKV infected cells reveal that GRP78 re-localises following infection and co-localises with Env. Depletion of GRP78 abrogated localisation of viral replication factories. Further experiments have shown that GRP78 is important for infection post entry and replication, and that putative GRP78 interactions partners are also required during infection. 2019-12-01 2020-08-19T14:43:51Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion EISSN: 2516-8290 https://repository.urosario.edu.co/handle/10336/27782 https://doi.org/10.1099/acmi.imav2019.po0021 eng info:eu-repo/semantics/openAccess application/pdf Microbiology Society Access Microbiology
institution EdocUR - Universidad del Rosario
collection DSpace
language Inglés (English)
topic Zika virus
ZIKV infection
Guillain-Barré syndrome
GRP78
Proteomics
Virus–cell interactions
spellingShingle Zika virus
ZIKV infection
Guillain-Barré syndrome
GRP78
Proteomics
Virus–cell interactions
Royle, Jamie
Ramírez-Santana, Carolina
Akpunarlieva, Snezhana
Donald, Claire L
Gestuveo, Rommel J
Anaya, Juan-Manuel
Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection
description Zika virus (ZIKV) is a member of the Flaviviridae family and was until recently a relatively obscure tropical disease. Subsequently, ZIKV has been shown to be the causative agent of fetal abnormalities and Guillain-Barré syndrome in outbreaks across the Americas and so efforts towards delineating important factors in the viral lifecycle have increased. Combining protein pull-down with mass spectrometry, it was found that ZIKV envelope (Env) interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78) in A549 cells. Flaviviruses such as Japanese encephalitis virus and dengue virus are known to co-opt ER resident proteins and members of the unfolded protein response, including GRP78, to enhance viral infectivity and propagation. The role these proteins play during the ZIKV lifecycle has yet to be elucidated. To determine the importance of this interaction during ZIKV infection, A549 cells were treated with GRP78-specific siRNAs prior to infection with a NanoLuc expressing reporter virus or a wild-type virus. Depletion of GRP78 significantly reduced both virus luciferase readings and viral titres, indicating that GRP78 is necessary for efficient infection of mammalian cell culture. In contrast, inhibition of GRP78 with small molecule inhibitors did not reduce ZIKV infection. Interestingly, immunofluorescence of ZIKV infected cells reveal that GRP78 re-localises following infection and co-localises with Env. Depletion of GRP78 abrogated localisation of viral replication factories. Further experiments have shown that GRP78 is important for infection post entry and replication, and that putative GRP78 interactions partners are also required during infection.
format Artículo (Article)
author Royle, Jamie
Ramírez-Santana, Carolina
Akpunarlieva, Snezhana
Donald, Claire L
Gestuveo, Rommel J
Anaya, Juan-Manuel
author_facet Royle, Jamie
Ramírez-Santana, Carolina
Akpunarlieva, Snezhana
Donald, Claire L
Gestuveo, Rommel J
Anaya, Juan-Manuel
author_sort Royle, Jamie
title Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection
title_short Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection
title_full Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection
title_fullStr Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection
title_full_unstemmed Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection
title_sort glucose regulated protein 78 (grp78) interacts with zika virus envelope and is required for a productive infection
publisher Microbiology Society
publishDate 2019
url https://repository.urosario.edu.co/handle/10336/27782
https://doi.org/10.1099/acmi.imav2019.po0021
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