Effects of radiation and latent virus on immune responses in a space flight model

Abstract

RATIONALE: We sought to develop a murine model that could assess the effects of space flight radiation and reactivation of latent virus infection to predict adverse health consequences for humans in interplanetary space travel.METHODS: Groups of 6 BALB/c female mice received whole body irradiation (3 Gy 137Cs) or sham irradiation on days 0 and/or 49, and 75 hemaglutinating units of murine polyomavirus (PyV) or PBS on day 1: A1, 3 Gy (day 0)/PyV/3 Gy (day 49); A2, 3 Gy/PyV/0 Gy; B1, 0 Gy/PyV/3 Gy; B2, 0 Gy/PyV/0 Gy; C, 3 Gy/PBS/0 Gy; and D, 0 Gy/PBS/0 Gy.RESULTS: PyV replication was detected by PCR in more A1 than B1 mice on days 10 and 20; both groups cleared PyV by day 49. Following irradiation on day 49, reactivated PyV was detected in more B1 (5/6) than A1 (2/6) mice. A1 had lower spleen weights and cell counts than other groups at all time points. In the initial time period (0-49 days), irradiation suppressed spleen cell proliferation to concanavalin A in A1, B1, and C except in B1 when the virus was cleared at day 20. PyV enhanced IFN-γ production by concanavalin A activated spleen cells in all groups: B1 > A1 > C, D (0-49 days), with variable results following irradiation on day 49. All differences, p < 0.05.CONCLUSIONS: This animal model of space flight suggests that the combined effects of radiation and latent virus replication will significantly affect T-cell mediated immunity that may lead to chronic viral infection and malignancy. RATIONALE: We sought to develop a murine model that could assess the effects of space flight radiation and reactivation of latent virus infection to predict adverse health consequences for humans in interplanetary space travel. METHODS: Groups of 6 BALB/c female mice received whole body irradiation (3 Gy 137Cs) or sham irradiation on days 0 and/or 49, and 75 hemaglutinating units of murine polyomavirus (PyV) or PBS on day 1: A1, 3 Gy (day 0)/PyV/3 Gy (day 49); A2, 3 Gy/PyV/0 Gy; B1, 0 Gy/PyV/3 Gy; B2, 0 Gy/PyV/0 Gy; C, 3 Gy/PBS/0 Gy; and D, 0 Gy/PBS/0 Gy. RESULTS: PyV replication was detected by PCR in more A1 than B1 mice on days 10 and 20; both groups cleared PyV by day 49. Following irradiation on day 49, reactivated PyV was detected in more B1 (5/6) than A1 (2/6) mice. A1 had lower spleen weights and cell counts than other groups at all time points. In the initial time period (0-49 days), irradiation suppressed spleen cell proliferation to concanavalin A in A1, B1, and C except in B1 when the virus was cleared at day 20. PyV enhanced IFN-γ production by concanavalin A activated spleen cells in all groups: B1 > A1 > C, D (0-49 days), with variable results following irradiation on day 49. All differences, p < 0.05. CONCLUSIONS: This animal model of space flight suggests that the combined effects of radiation and latent virus replication will significantly affect T-cell mediated immunity that may lead to chronic viral infection and malignancy.