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

Abstract

Background: The immunosuppressive effects of space flight radiation and reactivation of latent virus infections in human beings are largely unknown.

Objective: To develop a murine model that can predict the adverse effects of space flight radiation and reactivation of latent virus infection for human beings.

Methods: In experiment I, some BALB/c mice received whole-body gamma-irradiation (3 Gy) on day 0 and murine polyoma virus (PyV) on day 1. In experiment II, mice received irradiation (3 Gy) or none on days 0 and/or 49, and PyV or none on day 1: A1, 3 Gy/PyV/3 Gy; A2, 3 Gy/ PyV/0 Gy; B1, 0 Gy/PyV/3 Gy; B2, 0 Gy/ PyV/0 Gy; C, 3 Gy/0 PyV/0 Gy; and D, 0 Gy/0 PyV/0 Gy.

Results: In experiment I, PyV was detected by PCR more frequently in several host organs tested and for a longer period of time in irradiated than in control animals. In experiment II, PyV replication in the spleen was detected in A1>B1 mice on days 10 and 20; both groups cleared PyV by day 49. After irradiation on day 49, reactivated PyV was detected in more B1 than A1 mice. A1 mice had lower spleen weights and cell counts than other groups at all time points. From 0 to 49 days, irradiation suppressed spleen cell proliferation to concanavalin A in all irradiated groups except in B1 when the virus was cleared at day 20. PyV enhanced IFN-gamma production in all groups: B1>A1>C, D (0-49 days; all differences, P < .05).

Conclusion: This small animal model of space flight suggests that the combined effects of radiation and virus replication will significantly affect T-lymphocyte-mediated immunity that may lead to chronic viral infection and malignancy.