ER-shaping atlastin proteins act as central hubs to promote flavivirus replication and virion assembly

Christopher J. Neufeldt, Mirko Cortese, Pietro Scaturro, Berati Cerikan, Jeremy G. Wideman, Keisuke Tabata, Thaís Moraes, Olga Oleksiuk, Andreas Pichlmair, Ralf Bartenschlager

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Flaviviruses, including dengue virus and Zika virus, extensively remodel the cellular endomembrane network to generate replication organelles that promote viral genome replication and virus production. However, it remains unclear how these membranes and associated cellular proteins act during the virus cycle. Here, we show that atlastins (ATLs), a subset of ER resident proteins involved in neurodegenerative diseases, have dichotomous effects on flaviviruses—with ATL2 depletion leading to replication organelle defects, and ATL3 depletion to changes in virus production pathways. We characterized non-conserved functional domains in ATL paralogues and show that the ATL interactome is profoundly reprogrammed following dengue virus infection. Screen analysis confirmed non-redundant ATL functions and identified a specific role for ATL3, and its interactor ARF4, in vesicle trafficking and virion maturation. Our data identify ATLs as central hubs targeted by flaviviruses to establish their replication organelle and to achieve efficient virion maturation and secretion.

Original languageEnglish (US)
Pages (from-to)2416-2429
Number of pages14
JournalNature Microbiology
Volume4
Issue number12
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

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