The hypothesis of this project is that conditions of spaceflight – including solar radiation – damage the human immune system, leading to reactivation of latent viruses, increased viral infections and disease, and the possible development of cancer. Dr. Janet S. Butel’s laboratory is studying the immune system responses of mice in space-like conditions to determine the effect of space radiation on viral infections and virus-infected cells and to determine the ability of the mice to overcome viral infections and virus-induced cancers. This investigation will provide insights into the effects of spaceflight on infectious diseases and help develop methods for detecting, treating, and preventing virus reactivation.
Overview
Biology of Virus Infections: Radiation and Immunity
Principal Investigator:
Janet S. Butel, Ph.D.
Organization:
Baylor College of Medicine
Technical Summary
Spaceflight has been found to affect immune responses, and alterations in a normal immune response often have a major impact on the hosts ability to control infections. A question being explored is whether infectious diseases pose a medical risk to the success of long-duration space journeys. All humans are infected for life with latent and persistent viruses, and it is well-known that suppression of the immune system allows latent viruses to reactivate and multiply, which may cause disease in the person undergoing reactivation or in others to whom the virus is transmitted. To determine the effects of space radiation and hind limb unloading (HLU) on host control of virus infections and virus-induced cancers in a mouse model; and To characterize direct effects of radiation on viruses and virus-infected cells.
The general hypothesis is that conditions of long-duration spaceflight, including radiation, stress, isolation, containment and sleep deprivation, will alter human immune responses, leading to reactivation of latent viruses, increased viral infections and viral disease, and possible development of malignancies. We focused on reactivation and shedding of human herpesvirus EBV and human polyomaviruses, agents known to establish persistent infections and to undergo reactivation and cause disease, including cancer, when the host immune system is compromised. Animal models were used to study radiation effects on viral infections and host responses to those infections.
Specific Aims
Key Findings
Key findings of the project were from the mouse polyomavirus space radiation model we developed. A quantitative real-time polymerase chain reaction (RQ-PCR) assay was developed to measure murine polyomavirus (MuPyV) genome copies in infected animal tissues. This model showed that gamma-irradiation leads to immunosuppression, delayed clearance of primary virus infection, and reactivated latent viral infections. Both single high-dose and multiple low-doses of gamma-irradiation cause virus reactivation. HLU, which simulates aspects of weightlessness, was applied to the mouse model. HLU results in the loss of control of virus infection in a tissue-specific manner. Another finding was the identification of a herpesvirus EBV latent protein that might modulate the development of EBV-associated disease. In collaboration with Dr. Gerald Sonnenfeld, we carried out measurements of virus reactivations in volunteers participating in the NASA-sponsored Bed Rest and Immunity study, a model for the effects of spaceflight conditions on human physiology.
Earth Applications
This research addresses spaceflight-induced alterations in the immune system and their effects on host control of microbial infections. We have shown in several ground-based human models of spaceflight that even modest depressions in immune function correlate with virus reactivation and shedding. Using a mouse model, we have evidence of radiation-induced reactivation of viral infections and depression of host immune function. New information from these studies are applicable to the analysis of risks that may affect long-duration space travel. The knowledge gained from studies of virus infections in these test models will be applicable to Earth-bound individuals at risk of suffering similar virus reactivations and serious, sometimes life-threatening, consequences due to immunosuppression following organ transplantation or cancer chemotherapy, and during pregnancy, old age or AIDS. Studies of the role of herpesvirus EBV latent genes in human disease may lead to the development of novel antiviral drugs of benefit to individuals on Earth experiencing virus reactivations.
This project's funding ended in 2006