The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling
Summary: Flaviviruses are enveloped, positive-sensed single-stranded RNA viruses that remodel host membranes, incorporating both viral and host factors facilitating viral replication. In this study, we identified a key role for the membrane-bending host protein Reticulon 3.1 (RTN3.1A) during the rep...
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Elsevier
2017-11-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717315024 |
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author | Turgut E. Aktepe Susann Liebscher Julia E. Prier Cameron P. Simmons Jason M. Mackenzie |
author_facet | Turgut E. Aktepe Susann Liebscher Julia E. Prier Cameron P. Simmons Jason M. Mackenzie |
author_sort | Turgut E. Aktepe |
collection | DOAJ |
description | Summary: Flaviviruses are enveloped, positive-sensed single-stranded RNA viruses that remodel host membranes, incorporating both viral and host factors facilitating viral replication. In this study, we identified a key role for the membrane-bending host protein Reticulon 3.1 (RTN3.1A) during the replication cycle of three flaviviruses: West Nile virus (WNV), Dengue virus (DENV), and Zika virus (ZIKV). We observed that, during infection, RTN3.1A is redistributed and recruited to the viral replication complex, a recruitment facilitated via the WNV NS4A protein, however, not DENV or ZIKV NS4A. Critically, small interfering RNA (siRNA)-mediated knockdown of RTN3.1A expression attenuated WNV, DENV, and ZIKV replication and severely affected the stability and abundance of the NS4A protein, coinciding with a significant alternation and reduction of viral membrane structures in the endoplasmic reticulum. These observations identified a crucial role of RTN3.1A for the viral remodelling of host membranes during efficient flavivirus replication and the stabilization of viral proteins within the endoplasmic reticulum. : To study the underlying mechanism of flavivirus replication and membrane biogenesis, Aktepe et al. examine the role of the host membrane-shaping protein RTN3.1A during WNVKUN, DENV-2NGC, and ZIKVAFR replication. They find that RTN3.1A is required for NS4A-mediated membrane remodelling during biogenesis of the flavivirus replication complex. Keywords: virus replication, flavivirus, reticulon, membrane, host-virus interaction, NS4A, West Nile virus, Dengue virus, Zika virus |
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publishDate | 2017-11-01 |
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spelling | doaj.art-e2a4d7d0d8ac409b859d7f5c9dfd59fe2022-12-21T23:59:45ZengElsevierCell Reports2211-12472017-11-0121616391654The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane RemodellingTurgut E. Aktepe0Susann Liebscher1Julia E. Prier2Cameron P. Simmons3Jason M. Mackenzie4Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Corresponding authorSummary: Flaviviruses are enveloped, positive-sensed single-stranded RNA viruses that remodel host membranes, incorporating both viral and host factors facilitating viral replication. In this study, we identified a key role for the membrane-bending host protein Reticulon 3.1 (RTN3.1A) during the replication cycle of three flaviviruses: West Nile virus (WNV), Dengue virus (DENV), and Zika virus (ZIKV). We observed that, during infection, RTN3.1A is redistributed and recruited to the viral replication complex, a recruitment facilitated via the WNV NS4A protein, however, not DENV or ZIKV NS4A. Critically, small interfering RNA (siRNA)-mediated knockdown of RTN3.1A expression attenuated WNV, DENV, and ZIKV replication and severely affected the stability and abundance of the NS4A protein, coinciding with a significant alternation and reduction of viral membrane structures in the endoplasmic reticulum. These observations identified a crucial role of RTN3.1A for the viral remodelling of host membranes during efficient flavivirus replication and the stabilization of viral proteins within the endoplasmic reticulum. : To study the underlying mechanism of flavivirus replication and membrane biogenesis, Aktepe et al. examine the role of the host membrane-shaping protein RTN3.1A during WNVKUN, DENV-2NGC, and ZIKVAFR replication. They find that RTN3.1A is required for NS4A-mediated membrane remodelling during biogenesis of the flavivirus replication complex. Keywords: virus replication, flavivirus, reticulon, membrane, host-virus interaction, NS4A, West Nile virus, Dengue virus, Zika virushttp://www.sciencedirect.com/science/article/pii/S2211124717315024 |
spellingShingle | Turgut E. Aktepe Susann Liebscher Julia E. Prier Cameron P. Simmons Jason M. Mackenzie The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling Cell Reports |
title | The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling |
title_full | The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling |
title_fullStr | The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling |
title_full_unstemmed | The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling |
title_short | The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling |
title_sort | host protein reticulon 3 1a is utilized by flaviviruses to facilitate membrane remodelling |
url | http://www.sciencedirect.com/science/article/pii/S2211124717315024 |
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