| The inhibitors of nucleotide biosynthesis leflunomide, FK778, and mycophenolic acid activate hepatitis b virus replication In Vitro. | |
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MedLine Citation:
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PMID: 22271223 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The inhibitors of pyrimidine synthesis leflunomide and FK778 have been reported to exert broad antiviral effects, in addition to their immunosuppressive activities. Their possible therapeutic benefit for transplantation medicine is currently discussed, since they also block replication of human cytomegalovirus (CMV) and human polyomavirus BK (BKV) which both cause important complications in transplant recipients. Here, we show that leflunomide and FK778 strongly enhance hepatitis B virus (HBV) replication in vitro. This activity is shared by mycophenolic acid (MPA), an inhibitor of purine biosynthesis. Stimulation of HBV replication by these agents was linked to their inhibitory effects on de novo nucleotide biosynthesis since it could be efficiently counteracted by external nucleoside supply. Mechanistically, we found that MAP kinase (MAPK) p38 played a key role for the enhancement of HBV replication by leflunomide, FK778, and MPA. All three HBV-activating compounds increased p38 phosphorylation, in contrast to the HBV inhibitors telbivudine and cyclosporine A (CsA). Moreover, silencing of p38 expression via RNA interference (RNAi) efficiently counteracted the stimulatory effect of leflunomide, FK778, and MPA on HBV replication. In conclusion, our data indicate that - in contrast to their reported inhibitory effects on other viruses - both leflunomide and FK778 can augment HBV replication. Treatment with leflunomide, FK778, or MPA may bear the risk to enhance HBV replication in infected patients. (HEPATOLOGY 2012.). |
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Authors:
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Karin Hoppe-Seyler; Peter Sauer; Claudia Lohrey; Felix Hoppe-Seyler |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-23 |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 American Association for the Study of Liver Diseases. |
Affiliation:
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Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), Heidelberg, Germany. k.hoppe-seyler@dkfz.de. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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