Curative effect of split low dosage total-body irradiation on murine AIDS induced by Friend virus: the results and the possible mechanism.
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.
Shen
R N
RN
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121, USA.
Lu
L
L
Kaiser
H E
HE
Broxmeyer
H E
HE
D000818:Animals; D005622:Friend murine leukemia virus; D016158:Genes, p53; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007621:Karyotyping; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D013155:Spleen Focus-Forming Viruses / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014916:Whole-Body Irradiation
D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma