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Microbes Infect. 2013 Jan;15(1):45-55. doi: 10.1016/j.micinf.2012.10.003. Epub 2012 Oct 23.

Selective estrogen receptor modulators inhibit hepatitis C virus infection at multiple steps of the virus life cycle.

Author information

1
Department of Bioactive Molecules, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. murakami@nih.go.jp

Abstract

We screened for hepatitis C virus (HCV) inhibitors using the JFH-1 viral culture system and found that selective estrogen receptor modulators (SERMs), such as tamoxifen, clomifene, raloxifene, and other estrogen receptor α (ERα) antagonists, inhibited HCV infection. Treatment with SERMs for the first 2 h and treatment 2-24 h after viral inoculation reduced the production of HCV RNA. Treating persistently JFH-1 infected cells with SERMs resulted in a preferential inhibition of extracellular HCV RNA compared to intracellular HCV RNA. When we treated two subgenomic replicon cells, which harbor HCV genome genotype 2a (JFH-1) or genotype 1b, SERMs reduced HCV genome copies and viral protein NS5A. SERMs inhibited the entry of HCV pseudo-particle (HCVpp) genotypes 1a, 1b, 2a, 2b and 4 but did not inhibit vesicular stomatitis virus (VSV) entry. Further experiment using HCVpp indicated that tamoxifen affected both viral binding to cell and post-binding events including endocytosis. Taken together, SERMs seemed to target multiple steps of HCV viral life cycle: attachment, entry, replication, and post replication events. SERMs may be potential candidates for the treatment of HCV infection.

PMID:
23103222
DOI:
10.1016/j.micinf.2012.10.003
[Indexed for MEDLINE]

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