Chodosh J, Holder V P, Gan Y J, Belgaumi A, Sample J, Sixbey J W
Program in Viral Oncogenesis and Tumor Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
J Infect Dis. 1998 May;177(5):1194-201. doi: 10.1086/515290.
The hallmark of infection by human herpesviruses, life-long persistence in the host, is unaffected by current antiviral therapies effective against replication of virus. In vitro studies indicated that low concentrations of the ribonucleotide reductase inhibitor, hydroxyurea, completely eliminated Epstein-Barr virus (EBV) episomes from latently infected Burkitt's lymphoma (BL) cell subsets, providing the first example of chemotherapeutic eradication of a latent herpesvirus from any cell population. Unlike parental EBV-positive BL cells, virus-free cell progeny from one treated cell line no longer exhibited the malignant phenotype in tumorigenicity assays. Hydroxyurea-treated primary B lymphocytes immortalized by EBV ceased to proliferate as episomes were lost. The altered growth phenotype of both BL cells and immortalized primary B cells suggests that latent EBV is an appropriate and accessible therapeutic target for treatment of some EBV-induced lymphoproliferations.
人类疱疹病毒感染的标志是在宿主体内终身持续存在，这不受目前有效对抗病毒复制的抗病毒疗法的影响。体外研究表明，低浓度的核糖核苷酸还原酶抑制剂羟基脲可从潜伏感染的伯基特淋巴瘤（BL）细胞亚群中完全消除爱泼斯坦-巴尔病毒（EBV）附加体，这为从任何细胞群体中化疗根除潜伏性疱疹病毒提供了首个实例。与亲代EBV阳性BL细胞不同，来自一个经处理细胞系的无病毒细胞后代在致瘤性试验中不再表现出恶性表型。随着附加体丢失，经羟基脲处理的由EBV永生化的原代B淋巴细胞停止增殖。BL细胞和永生化原代B细胞生长表型的改变表明，潜伏性EBV是治疗某些EBV诱导的淋巴增殖的合适且可及的治疗靶点。
