Tamoxifen Protects from Vesicular Stomatitis Virus Infection
Tamoxifen Protects from Vesicular Stomatitis Virus Infection
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DOI：
10.3390/ph12040142
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发表时间：
2019-12-01
期刊：
影响因子：
4.6
通讯作者：
Lang, Judith
中科院分区：
文献类型：
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作者：
Cham, Lamin B.;Friedrich, Sarah-Kim;Lang, Judith
背景：三苯氧胺（TAM）是一种雌激素受体拮抗剂，广泛用于早期雌激素敏感性乳腺癌的辅助治疗。一些研究已经揭示了TAM的新的生物学靶点，其介导药物的雌激素受体非依赖性活性。最近，TAM在体外对人类免疫缺陷病毒（HIV）、丙型肝炎病毒（HCV）和单纯疱疹病毒（HSV-1）的复制的抗病毒活性被描述。在本研究中，我们的目的是探讨TAM对水泡性口炎病毒（VSV）感染的影响。方法：用不同浓度的TAM处理Vero细胞24 h后，用VSV感染Vero细胞。另外，在用VSV感染前1天和3天，用4 mg TAM预处理C57 BL/6小鼠。结果：TAM处理Vero细胞在体内外均能抑制VSV病毒的复制。TAM对VSV复制的抑制作用与增强的干扰素-I反应和刺激巨噬细胞相关。结论：TAM在体内外均具有抗VSV感染的作用。因此，这种抗病毒功能（作为TAM的有利副作用）可能会产生新的临床应用，如治疗耐药病毒感染，或作为标准抗病毒治疗的添加剂。
Background: Tamoxifen (TAM) is an estrogen-receptor antagonist, widely used in the adjuvant treatment of early stage estrogen-sensitive breast cancer. Several studies have revealed new biological targets of TAM that mediate the estrogen receptor independent activities of the drug. Recently, the antiviral activity of TAM on replication of human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Herpes simplex virus (HSV-1) in vitro was described. In the current study, we aimed to investigate the effect of TAM on infection with vesicular stomatitis virus (VSV). Methods: Vero cells were treated with different concentrations of TAM for 24 h and then infected with VSV. Additionally, C57BL/6 mice were pretreated with 4 mg TAM, one day and three days before infection with VSV. Results: Treatment of Vero cells with TAM suppressed the viral replication of VSV in vitro and in vivo. The inhibitory effect of TAM on VSV replication correlated with an enhanced interferon-I response and stimulation of macrophages. Conclusions: TAM was identified as being capable to protect from VSV infection in vitro and in vivo. Consequently, this antiviral function (as an advantageous side-effect of TAM) might give rise to new clinical applications, such as treatment of resistant virus infections, or serve as an add-on to standard antiviral therapy.