The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling

Turgut E Aktepe; Susann Liebscher; Julia E Prier; Cameron P Simmons; Jason M Mackenzie

Journal article

The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling

Turgut E Aktepe, Susann Liebscher, Julia E Prier, Cameron P Simmons, Jason M Mackenzie

CELL REPORTS | CELL PRESS | Published : 2017

DOI: 10.1016/j.celrep.2017.10.055

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Abstract

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 ZI..

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University of Melbourne Researchers

Jason Mackenzie Author Microbiology and Immunology

Turgut Aktepe Author Veterinary Biosciences

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Grants

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

We thank the Bio21 Institutes' Electron Microscopy Unit for their equipment and the expertise of Eric Hanssen, Zlatan Trifunovic, and Sergey Rubanov. We also thank Alexander Khromykh, Roy Hall, and Paul Young for generously providing the WNV and DENV antibodies; Julian Druce for providing ZIKV<INF>AFR</INF>; David Jans for providing DENV-2<INF>NGC</INF> and DENV antibodies; Daniel Watterson (University of Queensland) for advice with the DENV foci-forming assay; and Paulina Koszalka (University of Melbourne, Peter Doherty Institute for Infection and Immunity) for advice and aid with the cloning on DENV-2<INF>NGC</INF> and ZIKV<INF>AFR</INF> GFP-NS4A constructs. This research was supported by project grants (1004619 and 1081786) to J.M.M. from the National Health and Medical Research Council of Australia.