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...

Full description

Bibliographic Details
Main Authors: Turgut E. Aktepe, Susann Liebscher, Julia E. Prier, Cameron P. Simmons, Jason M. Mackenzie
Format: Article
Language:English
Published: Elsevier 2017-11-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717315024
_version_ 1818297623126212608
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
first_indexed 2024-12-13T04:22:22Z
format Article
id doaj.art-e2a4d7d0d8ac409b859d7f5c9dfd59fe
institution Directory Open Access Journal
issn 2211-1247
language English
last_indexed 2024-12-13T04:22:22Z
publishDate 2017-11-01
publisher Elsevier
record_format Article
series Cell Reports
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
work_keys_str_mv AT turguteaktepe thehostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT susannliebscher thehostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT juliaeprier thehostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT cameronpsimmons thehostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT jasonmmackenzie thehostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT turguteaktepe hostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT susannliebscher hostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT juliaeprier hostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT cameronpsimmons hostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling
AT jasonmmackenzie hostproteinreticulon31aisutilizedbyflavivirusestofacilitatemembraneremodelling