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

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1639-1654
Number of pages16
JournalCell Reports
Volume21
Issue number6
DOIs
Publication statusPublished - 7 Nov 2017
Externally publishedYes

Keywords

  • Dengue virus
  • flavivirus
  • host-virus interaction
  • membrane
  • NS4A
  • reticulon
  • virus replication
  • West Nile virus
  • Zika virus

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