Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH, USA.
Cell Cycle. 2011 Oct 1;10(19):3237-8. doi: 10.4161/cc.10.19.17299.
Reactivation of Kaposi sarcoma-associated herpesvirus (KSHV) from latency for lytic replication plays a pivotal role in the development of KS tumors. However, the physiological factors of KSHV reactivation in KS patients remain undefined. Two recent studies independently discovered that the reactive oxygen species (ROS) H(2)O(2) induces KSHV reactivation in latently infected cells, which can be inhibited by H(2)O(2)-specific antioxidants. H(2)O(2) not only directly induces KSHV reactivation but also is involved in spontaneous lytic replication as well as reactivation stimulated by TPA, hypoxia, and cytokines. Furthermore, in a xenograft-based primary effusion lymphoma (PEL) mouse model, in vivo KSHV reactivation is also H(2)O(2)-dependent and can be suppressed by antioxidants. Mechanistically, H(2)O(2) primarily activates the MAPK pathways to induce viral lytic gene expression and replication. This new finding defines a novel role of H(2)O(2) in KS tumorigenesis and highlights great potentials of using antioxidants and anti-inflammatory drugs for the prevention and treatment of KS tumors.
卡波西肉瘤相关疱疹病毒（KSHV）从潜伏状态重新激活进行裂解复制，在卡波西肉瘤肿瘤的发生发展中起关键作用。然而，KS 患者中 KSHV 重新激活的生理因素仍未明确。最近的两项研究独立发现，活性氧（ROS）H2O2 可诱导潜伏感染细胞中的 KSHV 重新激活，而 H2O2 特异性抗氧化剂可抑制这一过程。H2O2 不仅可直接诱导 KSHV 重新激活，还可参与自发性裂解复制，以及 TPA、低氧和细胞因子刺激的重新激活。此外，在基于异种移植的原发性渗出性淋巴瘤（PEL）小鼠模型中，体内 KSHV 重新激活也依赖于 H2O2，抗氧化剂可抑制其重新激活。在机制上，H2O2 主要通过激活 MAPK 通路诱导病毒裂解基因表达和复制。这一新发现定义了 H2O2 在卡波西肉瘤肿瘤发生中的新作用，并突出了使用抗氧化剂和抗炎药物预防和治疗卡波西肉瘤肿瘤的巨大潜力。
