Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection
Zika virus (ZIKV; Flaviviridae) is a mosquito-borne flavivirus shown to cause fetal abnormalities collectively known as congenital Zika syndrome and Guillain-Barré syndrome in recent outbreaks. Currently, there is no specific treatment or vaccine available, and more effort is needed to identify cell...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/5/524 |
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| author | Jamie Royle Carolina Ramírez-Santana Snezhana Akpunarlieva Claire L. Donald Rommel J. Gestuveo Juan-Manuel Anaya Andres Merits Richard Burchmore Alain Kohl Margus Varjak |
| author_facet | Jamie Royle Carolina Ramírez-Santana Snezhana Akpunarlieva Claire L. Donald Rommel J. Gestuveo Juan-Manuel Anaya Andres Merits Richard Burchmore Alain Kohl Margus Varjak |
| author_sort | Jamie Royle |
| collection | DOAJ |
| description | Zika virus (ZIKV; Flaviviridae) is a mosquito-borne flavivirus shown to cause fetal abnormalities collectively known as congenital Zika syndrome and Guillain-Barré syndrome in recent outbreaks. Currently, there is no specific treatment or vaccine available, and more effort is needed to identify cellular factors in the viral life cycle. Here, we investigated interactors of ZIKV envelope (E) protein by combining protein pull-down with mass spectrometry. We found that E interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78). Although other flaviviruses are known to co-opt ER resident proteins, including GRP78, to enhance viral infectivity, the role ER proteins play during the ZIKV life cycle is yet to be elucidated. We showed that GRP78 levels increased during ZIKV infection and localised to sites coincident with ZIKV E staining. Depletion of GRP78 using specific siRNAs significantly reduced reporter-virus luciferase readings, viral protein synthesis, and viral titres. Additionally, GRP78 depletion reduced the ability of ZIKV to disrupt host cell translation and altered the localisation of viral replication factories, though there was no effect on viral RNA synthesis. In summary, we showed GRP78 is a vital host-factor during ZIKV infection, which may be involved in the coordination of viral replication factories. |
| first_indexed | 2024-03-10T19:55:12Z |
| format | Article |
| id | doaj.art-202984884ace46b9828f8da1dccefa41 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T19:55:12Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-202984884ace46b9828f8da1dccefa412023-11-19T23:57:27ZengMDPI AGViruses1999-49152020-05-0112552410.3390/v12050524Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive InfectionJamie Royle0Carolina Ramírez-Santana1Snezhana Akpunarlieva2Claire L. Donald3Rommel J. Gestuveo4Juan-Manuel Anaya5Andres Merits6Richard Burchmore7Alain Kohl8Margus Varjak9MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKCenter for Autoimmune Diseases Research-CREA, School of Medicine and Health Sciences, Universidad del Rosario, 110010 Bogotá, ColombiaInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UKMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKCenter for Autoimmune Diseases Research-CREA, School of Medicine and Health Sciences, Universidad del Rosario, 110010 Bogotá, ColombiaInstitute of Technology, University of Tartu, 50411 Tartu, EstoniaInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UKMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKZika virus (ZIKV; Flaviviridae) is a mosquito-borne flavivirus shown to cause fetal abnormalities collectively known as congenital Zika syndrome and Guillain-Barré syndrome in recent outbreaks. Currently, there is no specific treatment or vaccine available, and more effort is needed to identify cellular factors in the viral life cycle. Here, we investigated interactors of ZIKV envelope (E) protein by combining protein pull-down with mass spectrometry. We found that E interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78). Although other flaviviruses are known to co-opt ER resident proteins, including GRP78, to enhance viral infectivity, the role ER proteins play during the ZIKV life cycle is yet to be elucidated. We showed that GRP78 levels increased during ZIKV infection and localised to sites coincident with ZIKV E staining. Depletion of GRP78 using specific siRNAs significantly reduced reporter-virus luciferase readings, viral protein synthesis, and viral titres. Additionally, GRP78 depletion reduced the ability of ZIKV to disrupt host cell translation and altered the localisation of viral replication factories, though there was no effect on viral RNA synthesis. In summary, we showed GRP78 is a vital host-factor during ZIKV infection, which may be involved in the coordination of viral replication factories.https://www.mdpi.com/1999-4915/12/5/524Zika virusproteomicsGRP78virus–cell interactions |
| spellingShingle | Jamie Royle Carolina Ramírez-Santana Snezhana Akpunarlieva Claire L. Donald Rommel J. Gestuveo Juan-Manuel Anaya Andres Merits Richard Burchmore Alain Kohl Margus Varjak Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection Viruses Zika virus proteomics GRP78 virus–cell interactions |
| title | Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection |
| title_full | Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection |
| title_fullStr | Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection |
| title_full_unstemmed | Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection |
| title_short | Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection |
| title_sort | glucose regulated protein 78 interacts with zika virus envelope protein and contributes to a productive infection |
| topic | Zika virus proteomics GRP78 virus–cell interactions |
| url | https://www.mdpi.com/1999-4915/12/5/524 |
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