Glaunsinger Britt, Ganem Don
Howard Hughes Medical Institute, Department of Microbiology, University of California, San Francisco, San Francisco, CA 94143, USA.
Mol Cell. 2004 Mar 12;13(5):713-23. doi: 10.1016/s1097-2765(04)00091-7.
The stimulation of host gene expression by lytic gene products of Kaposi's sarcoma-associated herpesvirus (KSHV) has been proposed to play a critical role in KS development. We show, however, that lytic KSHV infection strongly inhibits host gene expression early in infection by accelerating global mRNA turnover. This function is mediated by KSHV ORF37, a homolog of a DNA exonuclease widely present in other herpesviruses but which in KSHV has uniquely evolved additional functions that mediate its participation in RNA degradation. The ability of KSHV to inhibit host gene expression has important implications for models of KS pathogenesis that invoke activation of host transcription in lytically infected cells as a source of angiogenic or oncogenic factors.
卡波西肉瘤相关疱疹病毒（KSHV）的裂解基因产物对宿主基因表达的刺激作用被认为在卡波西肉瘤（KS）的发展中起关键作用。然而，我们发现，KSHV的裂解感染在感染早期通过加速整体mRNA周转来强烈抑制宿主基因表达。该功能由KSHV ORF37介导，ORF37是一种广泛存在于其他疱疹病毒中的DNA核酸外切酶的同源物，但在KSHV中它独特地进化出了额外的功能，介导其参与RNA降解。KSHV抑制宿主基因表达的能力对KS发病机制模型具有重要意义，这些模型将裂解感染细胞中宿主转录的激活作为血管生成或致癌因子的来源。
