Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy.
Aedes
Animals
Antiviral Agents
/ pharmacology
Apoptosis
/ immunology
Cell Line, Tumor
Chlorocebus aethiops
Cytokines
/ metabolism
Dengue
/ drug therapy
Dengue Virus
/ drug effects
Hep G2 Cells
Hepatocytes
/ pathology
Humans
Lipid Droplets
/ metabolism
Lipid Metabolism
Liver
/ pathology
Liver Diseases
/ drug therapy
Receptors, Virus
/ metabolism
Triglycerides
/ analysis
Vero Cells
Virus Replication
/ physiology
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
19
12
2019
accepted:
29
09
2020
revised:
04
12
2020
pubmed:
21
11
2020
medline:
26
1
2021
entrez:
20
11
2020
Statut:
epublish
Résumé
Suitable cell models are essential to advance our understanding of the pathogenesis of liver diseases and the development of therapeutic strategies. Primary human hepatocytes (PHHs), the most ideal hepatic model, are commercially available, but they are expensive and vary from lot-to-lot which confounds their utility. We have recently developed an immortalized hepatocyte-like cell line (imHC) from human mesenchymal stem cells, and tested it for use as a substitute model for hepatotropic infectious diseases. With a special interest in liver pathogenesis of viral infection, herein we determined the suitability of imHC as a host cell target for dengue virus (DENV) and as a model for anti-viral drug testing. We characterized the kinetics of DENV production, cellular responses to DENV infection (apoptosis, cytokine production and lipid droplet metabolism), and examined anti-viral drug effects in imHC cells with comparisons to the commonly used hepatoma cell lines (HepG2 and Huh-7) and PHHs. Our results showed that imHC cells had higher efficiencies in DENV replication and NS1 secretion as compared to HepG2 and Huh-7 cells. The kinetics of DENV infection in imHC cells showed a slower rate of apoptosis than the hepatoma cell lines and a certain similarity of cytokine profiles to PHHs. In imHC, DENV-induced alterations in levels of lipid droplets and triacylglycerols, a major component of lipid droplets, were more apparent than in hepatoma cell lines, suggesting active lipid metabolism in imHC. Significantly, responses to drugs with DENV inhibitory effects were greater in imHC cells than in HepG2 and Huh-7 cells. In conclusion, our findings suggest superior suitability of imHC as a new hepatocyte model for studying mechanisms underlying viral pathogenesis, liver diseases and drug effects.
Identifiants
pubmed: 33216752
doi: 10.1371/journal.pntd.0008835
pii: PNTD-D-19-02150
pmc: PMC7717553
doi:
Substances chimiques
Antiviral Agents
0
Cytokines
0
Receptors, Virus
0
Triglycerides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0008835Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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