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小热休克蛋白 20 和 27 的体外抗病毒作用:一种新的治疗方法。

In Vitro Anti-Viral Effects of Small Heat Shock Proteins 20 and 27: A Novel Therapeutic Approach.

机构信息

Department of Medical Lab Technology, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences; Tehran, Iran.

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Curr Pharm Biotechnol. 2019;20(12):1011-1017. doi: 10.2174/1389201020666190729104648.

Abstract

BACKGROUND

The protective effects of heat shock proteins (Hsps) were studied in some infectious and non-infectious diseases, but their specificity was slightly known in various disorders. Among Hsps, small Hsps (e.g. Hsp27 and Hsp20) have important roles in protein folding and translocation, and also in immunity.

METHODS

In this study, overexpression of Hsp20 and Hsp27 was performed by transfection of the plasmids encoding Hsp20 and Hsp27 (pEGFP-Hsp20 and pEGFP-Hsp27) into Huh7.5, Hela and Vero cells using Lipofectamine along with heat shock. Then, their anti-herpes simplex virus-1 (HSV-1), anti- human immunodeficiency virus-1 (HIV-1) and anti-hepatitis C virus (HCV) effects, as well as cytotoxicity, were evaluated in vitro, for the first time.

RESULTS

Our data showed that simultaneous treatment with Lipofectamine and heat shock augmented the rate of transfection and subsequently the expression of Hsps in these cells. Moreover, overexpression of Hsp20 in HCV-infected Huh7.5 cells, HIV-infected Hela cells and HSV-infected Vero cells reduced the replication of HCV, HIV and HSV, respectively. In contrast, overexpression of Hsp27 significantly decreased HSV replication similar to Hsp20, but it did not affect the replication of HIV and HCV.

CONCLUSION

Generally, Hsp20 was identified as a novel anti-HCV, anti-HSV and anti-HIV agent, but Hsp27 was efficient in the suppression of HSV infection. These Hsps may act through suppression of virus entry and/ or through interaction with viral proteins. Thus, it is necessary to determine their exact mechanisms in the near future.

摘要

背景

热休克蛋白(Hsps)在一些感染性和非传染性疾病中的保护作用已得到研究,但它们在各种疾病中的特异性尚不清楚。在 Hsps 中,小分子 Hsp(如 Hsp27 和 Hsp20)在蛋白质折叠和易位以及免疫中发挥重要作用。

方法

在这项研究中,通过脂质体转染将编码 Hsp20 和 Hsp27 的质粒(pEGFP-Hsp20 和 pEGFP-Hsp27)转染到 Huh7.5、Hela 和 Vero 细胞中,同时进行热休克,以实现 Hsp20 和 Hsp27 的过表达。然后,首次评估了它们在体外抗单纯疱疹病毒 1(HSV-1)、抗人类免疫缺陷病毒 1(HIV-1)和抗丙型肝炎病毒(HCV)的作用以及细胞毒性。

结果

我们的数据表明,脂质体和热休克的同时处理提高了这些细胞中转染的效率,进而提高了 Hsps 的表达。此外,在 HCV 感染的 Huh7.5 细胞、HIV 感染的 Hela 细胞和 HSV 感染的 Vero 细胞中过表达 Hsp20 分别降低了 HCV、HIV 和 HSV 的复制。相比之下,过表达 Hsp27 可显著降低 HSV 的复制,与 Hsp20 相似,但不影响 HIV 和 HCV 的复制。

结论

总体而言,Hsp20 被鉴定为一种新型抗 HCV、抗 HSV 和抗 HIV 药物,但 Hsp27 可有效抑制 HSV 感染。这些 Hsps 可能通过抑制病毒进入和/或通过与病毒蛋白相互作用而发挥作用。因此,有必要在不久的将来确定它们的确切机制。

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