Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, Illinois, USA.
J Virol. 2012 Dec;86(23):12871-8. doi: 10.1128/JVI.01981-12. Epub 2012 Sep 19.
Earlier studies reported that ICP0, a key regulatory protein encoded by herpes simplex virus 1 (HSV-1), binds ubiquitin-specific protease 7 (USP7). The fundamental conclusion of these studies is that depletion of USP7 destabilized ICP0, that ICP0 mediated the degradation of USP7, and that amino acid substitutions in ICP0 that abolished binding to USP7 significantly impaired the ability of HSV-1 to replicate. We show here that, indeed, depletion of USP7 leads to reduction of ICP0 and that USP7 is degraded in an ICP0-dependent manner. However, overexpression of USP7 or substitution in ICP0 of a single amino acid to abolish binding to USP7 accelerated the accumulation of viral mRNAs and proteins at early times after infection and had no deleterious effect on virus yields. A clue as to why USP7 is degraded emerged from the observation that, notwithstanding the accelerated expression of viral genes, the plaques formed by the mutant virus were very small, implying a defect in virus transmission from cell to cell.
早期研究报告称，单纯疱疹病毒 1（HSV-1）编码的关键调节蛋白 ICP0 与泛素特异性蛋白酶 7（USP7）结合。这些研究的基本结论是，USP7 的耗竭使 ICP0 不稳定，ICP0 介导了 USP7 的降解，并且使 ICP0 中与 USP7 结合的氨基酸取代显著削弱了 HSV-1 的复制能力。我们在这里表明，事实上，USP7 的耗竭导致 ICP0 的减少，并且 USP7 以 ICP0 依赖性方式降解。然而，USP7 的过表达或取代 ICP0 中单个氨基酸以消除与 USP7 的结合加速了感染后早期病毒 mRNA 和蛋白质的积累，并且对病毒产量没有有害影响。尽管病毒基因的表达加速，但由突变病毒形成的蚀斑非常小，这表明病毒从一个细胞传播到另一个细胞存在缺陷，这一观察结果为 USP7 被降解的原因提供了线索。
