Human Parainfluenza Virus Type 2 V Protein Modulates Iron Homeostasis.
FTH1
NCOA4
V protein
apoptosis
human parainfluenza virus type 2
iron homeostasis
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
24 02 2021
24 02 2021
Historique:
received:
23
09
2020
accepted:
15
12
2020
pubmed:
8
1
2021
medline:
6
5
2021
entrez:
7
1
2021
Statut:
epublish
Résumé
Intracellular iron concentration is tightly controlled for cell viability. It is known to affect the growth of several viruses, but the molecular mechanisms are not well understood. We found that iron chelators inhibit growth of human parainfluenza virus type 2 (hPIV-2). Furthermore, infection with hPIV-2 alters ferritin localization from granules to a homogenous distribution within cytoplasm of iron-stimulated cells. The V protein of hPIV-2 interacts with ferritin heavy chain 1 (FTH1), a ferritin subunit. It also binds to nuclear receptor coactivator 4 (NCOA4), which mediates autophagic degradation of ferritin, so-called ferritinophagy. V protein consequently interferes with interaction between FTH1 and NCOA4. hPIV-2 growth is inhibited in FTH1 knockdown cell line where severe hPIV-2-induced apoptosis is shown. In contrast, NCOA4 knockdown results in the promotion of hPIV-2 growth and limited apoptosis. Our data collectively suggest that hPIV-2 V protein inhibits FTH1-NCOA4 interaction and subsequent ferritinophagy. This iron homeostasis modulation allows infected cells to avoid apoptotic cell death, resulting in effective growth of hPIV-2.
Identifiants
pubmed: 33408172
pii: JVI.01861-20
doi: 10.1128/JVI.01861-20
pmc: PMC8094939
pii:
doi:
Substances chimiques
NCOA4 protein, human
0
Nuclear Receptor Coactivators
0
Viral Structural Proteins
0
Ferritins
9007-73-2
Iron
E1UOL152H7
FTH1 protein, human
EC 1.-
Oxidoreductases
EC 1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 American Society for Microbiology.
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