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人 BST-2 的结构域在抑制嗜性小鼠白血病病毒相关病毒释放中的作用。

The role of the structural domains of human BST-2 in inhibiting the release of xenotropic murine leukemia virus-related virus.

机构信息

MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.

出版信息

Biochem Biophys Res Commun. 2012 Nov 9;428(1):17-23. doi: 10.1016/j.bbrc.2012.10.001. Epub 2012 Oct 6.

DOI:10.1016/j.bbrc.2012.10.001
PMID:23047007
Abstract

BST-2 (bone marrow stromal cell antigen 2) is an interferon-inducible protein that inhibits the release of a variety of enveloped viruses by tethering viral particles to the cell surface. Xenotropic murine leukemia virus-related virus (XMRV) is a gamma-retrovirus that was derived from the recombination of two endogenous murine leukemia viruses during the production of a prostate cell line in mice. In this study, we observed that XMRV was highly sensitive to the inhibition by human BST-2. We were able to determine the structural domains of BST-2 that are essential to restrict XMRV, including the transmembrane domain, the coiled-coil ectodomain, the C-terminal glycosylphosphatidylinositol (GPI) anchor, the two putative N-linked glycosylation sites, and the three extracellular cysteine residues. Protease treatment effectively released XMRV particles into the supernatant, supporting the notion that BST-2 tethered nascent particles to the cell surface. These data suggest that BST-2 poses a strong restriction toward XMRV production.

摘要

BST-2(骨髓基质细胞抗原 2)是一种干扰素诱导蛋白,通过将病毒颗粒固定在细胞表面,抑制多种包膜病毒的释放。Xenotropic murine leukemia virus-related virus(XMRV)是一种γ逆转录病毒,它是在小鼠前列腺细胞系的产生过程中,由两种内源性鼠白血病病毒重组而来。在这项研究中,我们观察到 XMRV 对人 BST-2 的抑制作用非常敏感。我们能够确定限制 XMRV 的 BST-2 的结构域,包括跨膜域、卷曲螺旋外域、C 端糖基磷脂酰肌醇(GPI)锚、两个假定的 N-连接糖基化位点和三个细胞外半胱氨酸残基。蛋白酶处理可有效将 XMRV 颗粒释放到上清液中,这支持了 BST-2 将新生颗粒固定在细胞表面的观点。这些数据表明,BST-2 对 XMRV 的产生构成了强烈的限制。

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