Proteomics

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ER-shaping Atlastin proteins differentially contribute to flavivirus replication and assembly


ABSTRACT: Flaviviruses, including Dengue virus (DV) 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 upon DV 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Diploid Cell

SUBMITTER: Pietro Scaturro  

LAB HEAD: Ralf Bartenschlager

PROVIDER: PXD014640 | Pride | 2019-10-17

REPOSITORIES: Pride

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Publications

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

Neufeldt Christopher J CJ   Cortese Mirko M   Scaturro Pietro P   Cerikan Berati B   Wideman Jeremy G JG   Tabata Keisuke K   Moraes Thaís T   Oleksiuk Olga O   Pichlmair Andreas A   Bartenschlager Ralf R  

Nature microbiology 20191021 12


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 replica  ...[more]

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