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鉴定豚鼠 CMV gH/gL/GP129/GP131/GP133 复合物在感染和传播中的作用。

Characterization of the guinea pig CMV gH/gL/GP129/GP131/GP133 complex in infection and spread.

机构信息

Department of Infectious Diseases, Genentech, Inc./Hoffmann-LaRoche, Ltd., 1 DNA Way, South San Francisco, CA 94080, United States.

出版信息

Virology. 2013 Jun 20;441(1):75-84. doi: 10.1016/j.virol.2013.03.008. Epub 2013 Apr 4.

Abstract

In human cytomegalovirus (HCMV), the UL128-131A locus plays an essential role in cellular tropism and spread. Here, we report the complete annotation of the GP129-133 locus from guinea pig cytomegalovirus (GPCMV) and the discovery of the UL131A homolog, named GP133. We have found that similar to HCMV the GP129-133 proteins form a pentamer complex with the GPCMV glycoproteins gH and gL. In addition, we find that the GP129-133 proteins play a critical role in entry as the GP129-133 deletion mutant shows a defect in both endothelial and fibroblast cell entry. Although the GP129-133 deletion strain can propagate in vitro, we find that the deletion fails to spread in vivo. Interestingly, the wildtype strain can spontaneously give rise to the GP129-133 deletion strain during in vivo spread, suggesting genetic instability at this locus.

摘要

在人巨细胞病毒 (HCMV) 中,UL128-131A 基因座在细胞趋向性和传播中起着至关重要的作用。在这里,我们报告了豚鼠巨细胞病毒 (GPCMV) 的 GP129-133 基因座的完整注释,并发现了 UL131A 的同源物,命名为 GP133。我们发现,类似于 HCMV,GP129-133 蛋白与 GPCMV 糖蛋白 gH 和 gL 形成五聚体复合物。此外,我们发现 GP129-133 蛋白在进入过程中起着关键作用,因为 GP129-133 缺失突变体在内皮细胞和成纤维细胞进入中都存在缺陷。尽管 GP129-133 缺失株可以在体外繁殖,但我们发现该缺失株在体内无法传播。有趣的是,野生型株在体内传播过程中会自发产生 GP129-133 缺失株,表明该基因座存在遗传不稳定性。

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