Abstract | BACKGROUND & AIMS: METHODS: RESULTS:
Steroids had no significant effect on HEV replication. Cyclosporin A promoted replication of HEV in the subgenomic and infectious models. Knockdown of cyclophilin A and B increased levels of HEV genomic RNA by 4.0- ± 0.6-fold and 7.2- ± 1.9-fold, respectively (n = 6; P < .05). A high dose of FK506 promoted infection of liver cells with HEV. In contrast, MPA inhibited HEV replication. Incubation of cells with guanosine blocked the antiviral activity of MPA, indicating that the antiviral effects of this drug involve nucleotide depletion. The combination of MPA and ribavirin had a greater ability to inhibit HEV replication than MPA or ribavirin alone. CONCLUSIONS:
Cyclophilins A and B inhibit replication of HEV; this might explain the ability of cyclosporin A to promote HEV infection. On the other hand, the immunosuppressant MPA inhibits HEV replication. These findings should be considered when physicians select immunosuppressive therapies for recipients of organ transplants who are infected with HEV.
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Authors | Yijin Wang, Xinying Zhou, Yannick Debing, Kan Chen, Luc J W Van Der Laan, Johan Neyts, Harry L A Janssen, Herold J Metselaar, Maikel P Peppelenbosch, Qiuwei Pan |
Journal | Gastroenterology
(Gastroenterology)
Vol. 146
Issue 7
Pg. 1775-83
(Jun 2014)
ISSN: 1528-0012 [Electronic] United States |
PMID | 24582714
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Antiviral Agents
- Calcineurin Inhibitors
- Immunosuppressive Agents
- RNA, Viral
- cyclophilin B
- Ribavirin
- Cyclosporine
- Calcineurin
- Cyclophilin A
- Cyclophilins
- Mycophenolic Acid
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Topics |
- Antiviral Agents
(pharmacology)
- Calcineurin
(metabolism)
- Calcineurin Inhibitors
- Cell Line, Tumor
- Cyclophilin A
(genetics, metabolism)
- Cyclophilins
(genetics, metabolism)
- Cyclosporine
(pharmacology)
- Dose-Response Relationship, Drug
- HEK293 Cells
- Hepatitis E
(drug therapy, genetics, metabolism, virology)
- Hepatitis E virus
(drug effects, genetics, growth & development)
- Hepatitis, Chronic
(drug therapy, genetics, metabolism, virology)
- Humans
- Immunosuppressive Agents
(pharmacology)
- Mycophenolic Acid
(pharmacology)
- RNA Interference
- RNA, Viral
(biosynthesis)
- Ribavirin
(pharmacology)
- Time Factors
- Transfection
- Virus Replication
(drug effects)
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