马属动物睡眠蛋白11通过密码子使用依赖机制限制马传染性贫血病毒的产生。

Equine schlafen 11 restricts the production of equine infectious anemia virus via a codon usage-dependent mechanism.

作者信息

Lin Yue-Zhi, Sun Liu-Ke, Zhu Dan-Tong, Hu Zhe, Wang Xue-Feng, Du Cheng, Wang Yu-Hong, Wang Xiao-Jun, Zhou Jian-Hua

机构信息

Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China.

Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China; College of Wildlife Resources, Northeast Forestry University, Harbin, China.

出版信息

Virology. 2016 Aug;495:112-21. doi: 10.1016/j.virol.2016.04.024. Epub 2016 May 18.

DOI:10.1016/j.virol.2016.04.024

PMID:27200480

Abstract

Human schlafen11 is a novel restriction factor for HIV-1 based on bias regarding relative synonymous codon usage (RSCU). Here, we report the cloning of equine schlafen11 (eSLFN11) and the characteristics of its role in restricting the production of equine infectious anemia virus (EIAV), a retrovirus similar to HIV-1. Overexpression of eSLFN11 inhibited EIAV replication, whereas knockdown of endogenous eSLFN11 by siRNA enhanced the release of EIAV from its principal target cell. Notably, although eSLFN11 significantly suppressed expression of viral Gag protein and EIAV release into the culture medium, the levels of intracellular viral early gene proteins Tat and Rev and viral genomic RNA were unaffected. Coincidently, similar altered patterns of codon usage bias were observed for both the early and late genes of EIAV. Therefore, our data suggest that eSLFN11 restricts EIAV production by impairing viral mRNA translation via a mechanism that is similar to that employed by hSLFN11 for HIV-1.

摘要

基于相对同义密码子使用偏好（RSCU），人类schlafen11是一种新型的HIV-1限制因子。在此，我们报道了马schlafen11（eSLFN11）的克隆及其在限制马传染性贫血病毒（EIAV，一种与HIV-1相似的逆转录病毒）产生中的作用特性。eSLFN11的过表达抑制了EIAV复制，而通过小干扰RNA（siRNA）敲低内源性eSLFN11则增强了EIAV从其主要靶细胞中的释放。值得注意的是，尽管eSLFN11显著抑制病毒Gag蛋白的表达以及EIAV释放到培养基中，但细胞内病毒早期基因蛋白Tat和Rev以及病毒基因组RNA的水平并未受到影响。巧合的是，在EIAV的早期和晚期基因中均观察到了类似的密码子使用偏好改变模式。因此，我们的数据表明，eSLFN11通过一种与hSLFN11作用于HIV-1的机制相似的方式，即通过损害病毒mRNA翻译来限制EIAV的产生。