Cytomegalovirus and early-life irradiation synergize to erode protective immunity in aging (VIR5P.1034)

Abstract

Abstract Susceptibility to infectious disease increases with age, making it one of the leading causes of death in people over 65. The immune aging process may be accelerated by the presence of life-long latent infections, such as cytomegalovirus, that put a constant burden on the immune system. Theories of biological aging also suggest that immune cells may have defective functions in old age because of a lifetime of self-renewal, and DNA damage related senescence, among other factors. Sub-lethal whole-body irradiation results in dose-dependent death of immune cells throughout the body, forcing some peripheral self-renewal of surviving immune cells. We exposed mice to various sub-lethal irradiation doses (0Gy - 4Gy) in youth, and followed them for life. Some mice were also given life-long murine cytomegalovirus (MCMV) to reflect the most common latent virus in human populations. At the end of life, mice were vaccinated against, and then infected with, a potentially lethal dose of West Nile Virus (WNV). Neither MCMV, nor any dose of sub-lethal irradiation, independently altered survival following vaccination and WNV infection. However, mice that received a combination of 4Gy of irradiation in youth, and life-long MCMV infection, were less likely to survive WNV challenge. Mechanisms and implications for radiobiology, immune aging, and vaccine efficacy will be discussed.