Glaunsinger Britt, Chavez Leonard, Ganem Don
Department of Microbiology, Howard Hughes Medical Institute and G.W. Hooper Foundation, University of California, 513 Parnassus Ave., San Francisco, CA 94143-0552, USA.
J Virol. 2005 Jun;79(12):7396-401. doi: 10.1128/JVI.79.12.7396-7401.2005.
The Kaposi's sarcoma-associated herpesvirus (KSHV) SOX protein, encoded by ORF37, promotes shutoff of host cell gene expression during lytic viral replication by dramatically impairing mRNA accumulation. SOX is the KSHV homolog of the alkaline exonuclease of other herpesviruses, which has been shown to function as a DNase involved in processing and packaging the viral genome. Although the exonuclease activity of these proteins is widely conserved across all herpesviruses, the host shutoff activity observed for KSHV SOX is not. We show here that SOX expression sharply reduces the half-life of target mRNAs. Extensive mutational analysis reveals that the DNase and host shutoff activities of SOX are genetically separable. Lesions affecting the DNase activity cluster in conserved regions of the protein, but residues critical for mRNA degradation are not conserved across the viral family. Additionally, we present evidence suggesting that the two different functions of SOX occur within distinct cellular compartments-DNase activity in the nucleus and host shutoff activity in the cytoplasm.
卡波西肉瘤相关疱疹病毒（KSHV）的SOX蛋白由ORF37编码，在病毒裂解复制过程中，通过显著损害mRNA积累来促进宿主细胞基因表达的关闭。SOX是其他疱疹病毒碱性核酸外切酶的KSHV同源物，已证明其作为一种参与病毒基因组加工和包装的DNA酶发挥作用。尽管这些蛋白的核酸外切酶活性在所有疱疹病毒中广泛保守，但KSHV SOX所观察到的宿主关闭活性并非如此。我们在此表明，SOX的表达会大幅降低靶mRNA的半衰期。广泛的突变分析表明，SOX的DNA酶活性和宿主关闭活性在基因上是可分离的。影响DNA酶活性的损伤聚集在该蛋白的保守区域，但对mRNA降解至关重要的残基在病毒家族中并不保守。此外，我们提供的证据表明，SOX的两种不同功能发生在不同的细胞区室中——细胞核中的DNA酶活性和细胞质中的宿主关闭活性。
