Interferon-induced transmembrane proteins inhibit cell fusion mediated by trophoblast syncytins.
Antigens, Differentiation
/ chemistry
Antiviral Agents
/ pharmacology
Cell Fusion
Female
Gene Products, env
/ metabolism
HEK293 Cells
Humans
Interferon Type I
/ pharmacology
Membrane Proteins
/ antagonists & inhibitors
Placenta
/ cytology
Pregnancy
Pregnancy Proteins
/ metabolism
RNA Interference
RNA, Small Interfering
/ metabolism
RNA-Binding Proteins
/ antagonists & inhibitors
Trophoblasts
/ cytology
Virus Internalization
/ drug effects
Zika Virus
/ physiology
IFITM
IFITM1
IFITM2
IFITM3
Zika virus
cell fusion
fusion protein
influenza virus
interferon
interferon-induced transmembrane protein
membrane fusion
placenta
restriction factor
syncytin
trophoblast
virus
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
27 12 2019
27 12 2019
Historique:
received:
11
08
2019
revised:
11
11
2019
pubmed:
19
11
2019
medline:
23
6
2020
entrez:
19
11
2019
Statut:
ppublish
Résumé
Type I interferon (IFN) induced by virus infections during pregnancy can cause placental damage, but the mechanisms and identities of IFN-stimulated genes that are involved in this damage remain under investigation. The IFN-induced transmembrane proteins (IFITMs) inhibit virus infections by preventing virus membrane fusion with cells and by inhibiting fusion of infected cells (syncytialization). Fusion of placental trophoblasts via expression of endogenous retroviral fusogens known as syncytins forms the syncytiotrophoblast, a multinucleated cell structure essential for fetal development. We found here that IFN blocks fusion of BeWo human placental trophoblasts. Stably expressed IFITM1, -2, and -3 also blocked fusion of these trophoblasts while making them more resistant to virus infections. Conversely, stable IFITM knockdowns in BeWo trophoblasts increased their spontaneous fusion and allowed fusion in the presence of IFN while also making the cells more susceptible to virus infection. We additionally found that exogenous expression of IFITMs in HEK293T cells blocked fusion with cells expressing syncytin-1 or syncytin-2, confirming the ability of IFITMs to block individual syncytin-mediated fusion. Overall, our data indicate that IFITMs inhibit trophoblast fusion and suggest that there may be a critical balance between these antifusogenic effects and the beneficial antiviral effects of IFITMs in virus infections during pregnancy.
Identifiants
pubmed: 31735710
pii: S0021-9258(20)30008-9
doi: 10.1074/jbc.AC119.010611
pmc: PMC6937555
doi:
Substances chimiques
Antigens, Differentiation
0
Antiviral Agents
0
ERVFRD-1 protein, human
0
Gene Products, env
0
IFITM2 protein, human
0
IFITM3 protein, human
0
Interferon Type I
0
Membrane Proteins
0
Pregnancy Proteins
0
RNA, Small Interfering
0
RNA-Binding Proteins
0
leu-13 antigen
0
syncytin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19844-19851Subventions
Organisme : NIAID NIH HHS
ID : R01 AI130110
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI142256
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI146690
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI112542
Pays : United States
Informations de copyright
© 2019 Zani et al.
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