PMID- 33432690
OWN - NLM
STAT- MEDLINE
DCOM- 20211210
LR  - 20211214
IS  - 1462-5822 (Electronic)
IS  - 1462-5814 (Linking)
VI  - 23
IP  - 4
DP  - 2021 Apr
TI  - Valosin-containing protein ATPase activity regulates the morphogenesis of Zika 
      virus replication organelles and virus-induced cell death.
PG  - e13302
LID - 10.1111/cmi.13302 [doi]
AB  - With no available therapies, infections with Zika virus (ZIKV) constitute a major 
      public health concern as they can lead to congenital microcephaly. In order to 
      generate an intracellular environment favourable to viral replication, ZIKV 
      induces endomembrane remodelling and the morphogenesis of replication factories 
      via enigmatic mechanisms. In this study, we identified the AAA+ type ATPase 
      valosin-containing protein (VCP) as a cellular interaction partner of ZIKV 
      non-structural protein 4B (NS4B). Importantly, its pharmacological inhibition as 
      well as the expression of a VCP dominant-negative mutant impaired ZIKV 
      replication. In infected cells, VCP is relocalised to large ultrastructures 
      containing both NS4B and NS3, which are reminiscent of dengue virus convoluted 
      membranes. Moreover, short treatment with the VCP inhibitors NMS-873 or CB-5083 
      drastically decreased the abundance and size of ZIKV-induced convoluted 
      membranes. Furthermore, NMS-873 treatment inhibited ZIKV-induced mitochondria 
      elongation previously reported to be physically and functionally linked to 
      convoluted membranes in case of the closely related dengue virus. Finally, VCP 
      inhibition resulted in enhanced apoptosis of ZIKV-infected cells strongly 
      suggesting that convoluted membranes limit virus-induced cytopathic effects. 
      Altogether, this study identifies VCP as a host factor required for ZIKV life 
      cycle and more precisely, for the maintenance of viral replication factories. Our 
      data further support a model in which convoluted membranes regulate ZIKV life 
      cycle by impacting on mitochondrial functions and ZIKV-induced death signals in 
      order to create a cytoplasmic environment favourable to viral replication.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Anton, Anais
AU  - Anton A
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
FAU - Mazeaud, Clement
AU  - Mazeaud C
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
FAU - Freppel, Wesley
AU  - Freppel W
AUID- ORCID: 0000-0003-3628-0465
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
FAU - Gilbert, Claudia
AU  - Gilbert C
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
FAU - Tremblay, Nicolas
AU  - Tremblay N
AUID- ORCID: 0000-0003-4246-7189
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
FAU - Sow, Aissatou Aicha
AU  - Sow AA
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
FAU - Roy, Marie
AU  - Roy M
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
FAU - Rodrigue-Gervais, Ian Gael
AU  - Rodrigue-Gervais IG
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
FAU - Chatel-Chaix, Laurent
AU  - Chatel-Chaix L
AUID- ORCID: 0000-0002-7390-8250
AD  - Centre Armand-Frappier Sante Biotechnologie, Institut National de la Recherche 
      Scientifique, Laval, Quebec, Canada.
AD  - Center of Excellence in Research on Orphan Diseases-Courtois Foundation 
      (CERMO-FC), Montreal, Quebec, Canada.
AD  - Reseau Intersectoriel de Recherche en Sante de l'Universite du Quebec (RISUQ), 
      Quebec, Canada.
LA  - eng
GR  - ICS154142/CIHR/Canada
GR  - ICS154142/CIHR/Canada
GR  - PJT153020/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210111
PL  - India
TA  - Cell Microbiol
JT  - Cellular microbiology
JID - 100883691
RN  - 0 (Acetanilides)
RN  - 0 (Benzothiazoles)
RN  - 0 (CB-5083)
RN  - 0 (Indoles)
RN  - 0 (NMS-873)
RN  - 0 (Pyrimidines)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.4.6 (Valosin Containing Protein)
SB  - IM
MH  - Acetanilides/pharmacology
MH  - Adenosine Triphosphatases/genetics/*metabolism
MH  - Animals
MH  - *Apoptosis
MH  - Benzothiazoles/pharmacology
MH  - Cell Line, Tumor
MH  - Chlorocebus aethiops
MH  - *Gene Expression Regulation
MH  - HEK293 Cells
MH  - Host Microbial Interactions/drug effects/genetics
MH  - Humans
MH  - Indoles/pharmacology
MH  - Mitochondria/drug effects/metabolism/virology
MH  - Pyrimidines/pharmacology
MH  - Valosin Containing Protein/antagonists & inhibitors/*genetics/*metabolism
MH  - Vero Cells
MH  - Zika Virus/*genetics/*physiology
EDAT- 2021/01/13 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/01/12 06:15
PHST- 2020/03/01 00:00 [received]
PHST- 2020/12/01 00:00 [revised]
PHST- 2020/12/15 00:00 [accepted]
PHST- 2021/01/13 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/01/12 06:15 [entrez]
AID - 10.1111/cmi.13302 [doi]
PST - ppublish
SO  - Cell Microbiol. 2021 Apr;23(4):e13302. doi: 10.1111/cmi.13302. Epub 2021 Jan 11.