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- Title
25-Hydroxyvitamin D3 suppresses hepatitis C virus production.
- Authors
Matsumura, Takuya; Kato, Takanobu; Sugiyama, Nao; Tasaka-Fujita, Megumi; Murayama, Asako; Masaki, Takahiro; Wakita, Takaji; Imawari, Michio
- Abstract
Because the current interferon (IFN)-based treatment for hepatitis C virus (HCV) infection has a therapeutic limitation and side effects, a more efficient therapeutic strategy is desired. Recent studies show that supplementation of vitamin D significantly improves sustained viral response via IFN-based therapy. However, mechanisms and an active molecular form of vitamin D for its anti-HCV effects have not been fully clarified. To address these questions, we infected HuH-7 cells with cell culture-generated HCV in the presence or absence of vitamin D(3) or its metabolites. To our surprise, 25-hydroxyvitamin D(3) [25(OH)D(3) ], but not vitamin D(3) or 1,25-dihydroxyvitamin D(3) , reduced the extra- and intracellular levels of HCV core antigen in a concentration-dependent manner. Single-cycle virus production assay with a CD81-negative cell line reveals that the inhibitory effect of 25(OH)D(3) is at the level of infectious virus assembly but not entry or replication. Long-term 25(OH)D(3) treatment generates a HCV mutant with acquired resistance to 25(OH)D(3) , and this mutation resulting in a N1279Y substitution in the nonstructural region 3 helicase domain is responsible for the resistance.
- Publication
Hepatology (Baltimore, Md.), 2012, Vol 56, Issue 4, p1231
- ISSN
1527-3350
- Publication type
Journal Article
- DOI
10.1002/hep.25763