Effects of low dose gamma radiation on the human immunodeficiency virus-1

Lymphocytes are highly radiosensitive and the major host cells of HIV-1. To evaluate the effects of low doses of gamma radiation on HIV-1 replication, models of acute HIV-1 infection, PBMCs of HIV-1-infected patients and HIV-1 positive cell lines were used. The results demonstrated that HTLV-IIIB virus (laboratory strain of HIV-1) replication significantly increased in cultures initiated from PBMCs exposed to gamma radiation at the dose of 50 cGy given prior to PHA stimulation and acute infection. Similar results were also obtained in purified CD4 cells. The mechanism underlying these observations may be related to oxidative stress since pre-infection treatment with 35 nM H₂O₂ increased the susceptibility of PBMCs to acute infection in a similar way. Exposure of the cells to gamma radiation after in vitro infection had no significant stimulatory effect. In HIV-1-infected PBMCs taken from a patient with high levels of HIV-1 replication in the plasma, viral replication was clearly stimulated by exposure to 50 cGy as compared to the non-irradiated control. The highest stimulatory effect was found when acute infection following host cell irradiation was delayed for 24 hours. It seems that this stimulatory effect is due to host cells becoming more susceptible to viral infection rather than latent viral DNA becoming transcriptionally active following low doses of ionizing radiation. Radiation effects on viral replication are closely related to its timing, the stimulatory effects being more obvious in the early stage of the viral life cycle (perhaps before the integration of viral DNA). The stimulatory response of low doses of gamma radiation on viral replication is a trigger-type rather than dose-dependent response. Results support a mechanism in which low doses of gamma exposure induce IL2α receptors on the surface of mitogen-stimulated PBMCs that makes cells more susceptible to virus infection. Viral replication is continuous throughout the course of HIV-1 infection and a delicate balance among a wide array of host factors likely determines the net rate of viral replication. In light of our results, we recommend that extra precautions be considered when treating HIV-1 infected patients with radiation for medical purposes.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat