PMID- 33147489
OWN - NLM
STAT- MEDLINE
DCOM- 20210519
LR  - 20211204
IS  - 1875-9777 (Electronic)
IS  - 1934-5909 (Print)
IS  - 1875-9777 (Linking)
VI  - 27
IP  - 6
DP  - 2020 Dec 3
TI  - Multimerization of Zika Virus-NS5 Causes Ciliopathy and Forces Premature 
      Neurogenesis.
PG  - 920-936.e8
LID - S1934-5909(20)30496-3 [pii]
LID - 10.1016/j.stem.2020.10.002 [doi]
AB  - Zika virus (ZikV) is a flavivirus that infects neural tissues, causing congenital 
      microcephaly. ZikV has evolved multiple mechanisms to restrict proliferation and 
      enhance cell death, although the underlying cellular events involved remain 
      unclear. Here we show that the ZikV-NS5 protein interacts with host proteins at 
      the base of the primary cilia in neural progenitor cells, causing an atypical 
      non-genetic ciliopathy and premature neuron delamination. Furthermore, in human 
      microcephalic fetal brain tissue, ZikV-NS5 persists at the base of the motile 
      cilia in ependymal cells, which also exhibit a severe ciliopathy. Although the 
      enzymatic activity of ZikV-NS5 appears to be dispensable, the amino acids Y25, 
      K28, and K29 that are involved in NS5 oligomerization are essential for 
      localization and interaction with components of the cilium base, promoting 
      ciliopathy and premature neurogenesis. These findings lay the foundation for 
      therapies that target ZikV-NS5 multimerization and prevent the developmental 
      malformations associated with congenital Zika syndrome.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Saade, Murielle
AU  - Saade M
AD  - Developmental Biology Department, Instituto de Biologia Molecular de Barcelona 
      (IBMB-CSIC), Parc Cientific de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, 
      Spain. Electronic address: msabmc@ibmb.csic.es.
FAU - Ferrero, Diego S
AU  - Ferrero DS
AD  - Structural Biology Department, Instituto de Biologia Molecular de Barcelona 
      (IBMB-CSIC), Parc Cientific de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, 
      Spain.
FAU - Blanco-Ameijeiras, Jose
AU  - Blanco-Ameijeiras J
AD  - Developmental Biology Department, Instituto de Biologia Molecular de Barcelona 
      (IBMB-CSIC), Parc Cientific de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, 
      Spain.
FAU - Gonzalez-Gobartt, Elena
AU  - Gonzalez-Gobartt E
AD  - Developmental Biology Department, Instituto de Biologia Molecular de Barcelona 
      (IBMB-CSIC), Parc Cientific de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, 
      Spain.
FAU - Flores-Mendez, Marco
AU  - Flores-Mendez M
AD  - Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The 
      Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of 
      Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 
      19104, USA.
FAU - Ruiz-Arroyo, Victor M
AU  - Ruiz-Arroyo VM
AD  - Structural Biology Department, Instituto de Biologia Molecular de Barcelona 
      (IBMB-CSIC), Parc Cientific de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, 
      Spain.
FAU - Martinez-Saez, Elena
AU  - Martinez-Saez E
AD  - Department of Pathology, Vall d'Hebron University Hospital, Translational 
      Molecular Pathology, Vall d'Hebron Institute of Research (VHIR), Universitat 
      Autonoma de Barcelona and Spanish Biomedical Research Network Centre in Oncology 
      (CIBERONC), Barcelona 08035, Spain.
FAU - Ramon Y Cajal, Santiago
AU  - Ramon Y Cajal S
AD  - Department of Pathology, Vall d'Hebron University Hospital, Translational 
      Molecular Pathology, Vall d'Hebron Institute of Research (VHIR), Universitat 
      Autonoma de Barcelona and Spanish Biomedical Research Network Centre in Oncology 
      (CIBERONC), Barcelona 08035, Spain.
FAU - Akizu, Naiara
AU  - Akizu N
AD  - Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The 
      Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of 
      Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 
      19104, USA.
FAU - Verdaguer, Nuria
AU  - Verdaguer N
AD  - Structural Biology Department, Instituto de Biologia Molecular de Barcelona 
      (IBMB-CSIC), Parc Cientific de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, 
      Spain.
FAU - Marti, Elisa
AU  - Marti E
AD  - Developmental Biology Department, Instituto de Biologia Molecular de Barcelona 
      (IBMB-CSIC), Parc Cientific de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, 
      Spain. Electronic address: emgbmc@ibmb.csic.es.
LA  - eng
GR  - R00 NS089859/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201103
PL  - United States
TA  - Cell Stem Cell
JT  - Cell stem cell
JID - 101311472
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
CIN - Nat Rev Microbiol. 2021 Jan;19(1):2. PMID: 33154572
MH  - *Ciliopathies
MH  - Humans
MH  - Neurogenesis
MH  - Viral Nonstructural Proteins
MH  - *Zika Virus
MH  - *Zika Virus Infection
PMC - PMC7718408
MID - NIHMS1638977
OTO - NOTNLM
OT  - CNS growth
OT  - Zika virus
OT  - centrosome
OT  - ciliopathy
OT  - microcephaly
OT  - neural progenitor cell
COIS- Declaration of Interests The authors declare no competing interests.
EDAT- 2020/11/05 06:00
MHDA- 2021/05/20 06:00
PMCR- 2021/12/03
CRDT- 2020/11/04 20:07
PHST- 2020/03/25 00:00 [received]
PHST- 2020/08/16 00:00 [revised]
PHST- 2020/10/08 00:00 [accepted]
PHST- 2020/11/05 06:00 [pubmed]
PHST- 2021/05/20 06:00 [medline]
PHST- 2020/11/04 20:07 [entrez]
PHST- 2021/12/03 00:00 [pmc-release]
AID - S1934-5909(20)30496-3 [pii]
AID - 10.1016/j.stem.2020.10.002 [doi]
PST - ppublish
SO  - Cell Stem Cell. 2020 Dec 3;27(6):920-936.e8. doi: 10.1016/j.stem.2020.10.002. 
      Epub 2020 Nov 3.