TY - JOUR
T1 - ER-shaping atlastin proteins act as central hubs to promote flavivirus replication and virion assembly
AU - Neufeldt, Christopher J.
AU - Cortese, Mirko
AU - Scaturro, Pietro
AU - Cerikan, Berati
AU - Wideman, Jeremy G.
AU - Tabata, Keisuke
AU - Moraes, Thaís
AU - Oleksiuk, Olga
AU - Pichlmair, Andreas
AU - Bartenschlager, Ralf
N1 - Funding Information:
We thank A. Ruggieri, L. Chatel-Chaix and M. Joyce for constructive scientific discussions and valuable comments. We also thank U. Haselmann, M. Bartenschlager, I. Paron, A. Piras and S. Kallis for excellent technical support. We acknowledge the Electron Microscopy Core Facility at Heidelberg University and the Infectious Diseases Imaging Platform (IDIP) at the Center for Integrative Infectious Disease Research, Heidelberg, Germany, for expert assistance and access to their equipment as well as the Department of Proteomics and Signal Transduction of the Max-Planck Institute of Biochemistry for continuous and generous support. We thank the European Virus Archive (EVAg, France) for provision of ZV strains, J. Schmidt-Chanasit for providing WNV strains, F. Weber for providing the RVFV isolate, D. Trono for providing the lentiviral transduction system and M. Stanifer for providing the VSVg constructs. This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB1129, TP11 and BA1505/8-1, both to R.B., and TRR179 and TP11 to A.P.) and the ERC (StG iVIP 331339, CoG ProDAP 817798) to A.P. C.J.N. was supported in part by a European Molecular Biology Organization (EMBO) Long-Term Fellowship (ALTF 466-2016).
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41564-019-0586-3
DO - 10.1038/s41564-019-0586-3
M3 - Article
C2 - 31636417
AN - SCOPUS:85074603907
SN - 2058-5276
VL - 4
SP - 2416
EP - 2429
JO - Nature Microbiology
JF - Nature Microbiology
IS - 12
ER -