Kim Soo Jin, Wong Paul K Y
Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Smithville, TX, USA.
J Gen Virol. 2015 Jan;96(Pt 1):144-149. doi: 10.1099/vir.0.070391-0. Epub 2014 Sep 24.
Infection of astrocytes by the neuropathogenic mutant of Moloney murine leukemia virus, ts1, exhibits increased levels of reactive oxygen species (ROS) and signs of oxidative stress compared with uninfected astrocytes. Previously, we have demonstrated that ts1 infection caused two separate events of ROS upregulation. The first upregulation occurs during early viral establishment in host cells and the second during the virus-mediated apoptotic process. In this study, we show that virus-mediated ROS upregulation activates the protein kinase, ataxia telangiectasia mutated, which in turn phosphorylates serine 15 on p53. This activation of p53 however, is unlikely associated with ts1-induced cell death. Rather p53 appears to be involved in suppressing intracellular ROS levels in astrocytes under oxidative stress. The activated p53 appears to delay retroviral gene expression by suppressing NADPH oxidase, a superoxide-producing enzyme. These results suggest that p53 plays a role as a retrovirus-mediated oxidative stress modulator.
与未感染的星形胶质细胞相比，莫洛尼鼠白血病病毒神经致病突变体ts1感染星形胶质细胞后，活性氧（ROS）水平升高，并出现氧化应激迹象。此前，我们已经证明ts1感染会引发ROS上调的两个独立事件。第一次上调发生在病毒在宿主细胞中早期建立期间，第二次发生在病毒介导的凋亡过程中。在本研究中，我们表明病毒介导的ROS上调激活了蛋白激酶共济失调毛细血管扩张突变蛋白（ATM），进而使p53的丝氨酸15位点磷酸化。然而，这种p53的激活不太可能与ts1诱导的细胞死亡相关。相反，p53似乎参与了在氧化应激下抑制星形胶质细胞内的ROS水平。激活的p53似乎通过抑制作为超氧化物产生酶的NADPH氧化酶来延迟逆转录病毒基因表达。这些结果表明，p53作为逆转录病毒介导的氧化应激调节剂发挥作用。
