Lembo David, Brune Wolfram
Department of Clinical and Biological Sciences, University of Turin, S Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
Trends Biochem Sci. 2009 Jan;34(1):25-32. doi: 10.1016/j.tibs.2008.09.008. Epub 2008 Nov 5.
Ribonucleotide reductase (RNR), a crucial enzyme for nucleotide anabolism, is encoded by all living organisms and by large DNA viruses such as the herpesviruses. Surprisingly, the beta-herpesvirus subfamily RNR R1 subunit homologues are catalytically inactive and their function remained enigmatic for many years. Recent work sheds light on the function of M45, the murine cytomegalovirus R1 homologue; during viral evolution, M45 apparently lost its original RNR activity but gained the ability, via inhibiting RIP1, a cellular adaptor protein, to block cellular signaling pathways involved in innate immunity and inflammation. The discovery of this novel mechanism of viral immune subversion provides further support to the concept of evolutionary tinkering.
核糖核苷酸还原酶（RNR）是核苷酸合成代谢中的一种关键酶，所有生物体以及疱疹病毒等大型DNA病毒都对其进行编码。令人惊讶的是，β-疱疹病毒亚科的RNR R1亚基同源物没有催化活性，其功能多年来一直成谜。最近的研究揭示了小鼠巨细胞病毒R1同源物M45的功能；在病毒进化过程中，M45显然失去了其原有的RNR活性，但通过抑制细胞衔接蛋白RIP1获得了阻断参与先天免疫和炎症的细胞信号通路的能力。这种病毒免疫颠覆新机制的发现为进化修补概念提供了进一步支持。
