Shen R N, Lu L, Kaiser H E, Broxmeyer H E
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121, USA.
In Vivo. 1996 Mar-Apr;10(2):191-9.
Mice infected with Friend Leukemia Virus (FLV) rapidly develop erythroleukemia and severe immune deficiency which resembles human AIDS. We have reported that mice infected with a lethal dose of FLV can be 100% cured by 150 cGy total body irradiation (TBI). This curative effect was associated with restoration of cellular immunity which was compromised by the virus. This restoration may result from activation of the IFN-gamma system and IL-2 production. Our research work further demonstrated that no spleen focus-forming virus (SFFV) specific mRNAs, no 6.0kb SFFV fragments and SFFV envelope glycoproteins were detectable in FLV-infected mice treated with low dose TBI. Predicated on our report, del Regato has initiated clinical trials to treat AIDS patients with low dose TBI. The preliminary results are encouraging and the study is continuing. We have also studied the effects of low dose TBI on the expression of the P53 gene. The results show loss or inactivation of P53 tumor suppressor genes in FLV-infected mice, but P53 expression was restored in FLV-infected mice treated by low dose TBI. It is intriguing to speculate that in the curative effect of low dose TBI on mice infected with retrovirus, the P53 tumor suppressor gene may play an important role. It would be of interest to see if this type of treatment, which was well tolerated by mice, would be beneficial in other types of virally induced disease, including AIDS.
感染了弗瑞德白血病病毒（FLV）的小鼠会迅速患上红白血病和严重的免疫缺陷，这类似于人类艾滋病。我们曾报道，感染致死剂量FLV的小鼠经150 cGy全身照射（TBI）后可100%治愈。这种治愈效果与被病毒损害的细胞免疫的恢复有关。这种恢复可能源于干扰素-γ系统的激活和白细胞介素-2的产生。我们的研究工作进一步表明，在用低剂量TBI治疗的FLV感染小鼠中，未检测到脾脏灶形成病毒（SFFV）特异性mRNA、6.0kb SFFV片段和SFFV包膜糖蛋白。基于我们的报告，德尔·雷加托已启动临床试验，用低剂量TBI治疗艾滋病患者。初步结果令人鼓舞，研究仍在继续。我们还研究了低剂量TBI对P53基因表达的影响。结果显示，FLV感染小鼠中P53肿瘤抑制基因缺失或失活，但经低剂量TBI治疗的FLV感染小鼠中P53表达得以恢复。有趣的是，可以推测在低剂量TBI对感染逆转录病毒小鼠的治愈作用中，P53肿瘤抑制基因可能起重要作用。看看这种小鼠耐受性良好的治疗方法是否对包括艾滋病在内的其他类型病毒诱导疾病有益，将是一件很有意思的事情。
