A major concern associated with long-duration space flight is the possibility of infectious diseases posing an unacceptable medical risk to crew members. One major hypothesis addressed in this project was that space flight will cause alterations in the immune system that will allow latent viruses that are endogenous in the human population to reactivate and shed to higher levels than normal, which may affect the health of crew members. The second major hypothesis examined was that the effects of space flight will alter the mucosal immune system, the first line of defense against many microbial infections, including herpesviruses, polyomaviruses, and gastroenteritis viruses, rendering crew members more susceptible to virus infections across the mucosa.
We focused the virus studies on the human herpesviruses and polyomaviruses, important pathogens known to establish latent infections in most of the human population. Both primary infection and reactivation from latent infection with these groups of viruses (especially certain herpesviruses) can cause a variety of illnesses that result in morbidity and, occasionally, mortality. Both herpesviruses and polyomaviruses have been associated with human cancer. Whereas normal individuals display minimal consequences from latent viral infections, events which alter immune function (such as immunosuppressive therapy following solid organ transplantation) are known to increase the risk of complications as a result of viral reactivations. As this was a new research effort for the project team, initial efforts included development of dedicated laboratory facilities, training of personnel, establishment of collaborations, and development of assays. Special cages were tested, design modified, and then fabricated for the antiorthostatic suspension (AOS) mouse mucosal immunity studies.
The strategy of this project was to measure the frequency and magnitude of viral shedding from humans participating in activities that serve as ground-based models of space flight conditions. First, however, using sensitive polymerase chain reaction (PCR)-based assays for herpesviruses and for polyomaviruses, we established baseline patterns of virus reactivation and shedding in normal healthy volunteers (n = 30) in a one-year-long longitudinal study. We found that normal individuals over age 40 frequently shed polyomavirus JCV in urine, and some normal individuals shed high levels of herpesvirus EBV in saliva, indicating that viral contamination within a spacecraft is an issue to be considered. We then organized collaborations involving several ground-based human models that mimic certain aspects of space flight. These included wintering-over in Antarctica; a Russian closed chamber study in which individuals were confined within a space-craft-like chamber on the ground; a sleep-disruption model; and HIV-infected individuals, a medical condition in which patients suffer immunosuppression due to infection with HIV, the AIDS virus. Analyses of specimens from these space analog models are still in progress, but there is preliminary evidence of increased viral reactivation and shedding, suggesting that space flight conditions can alter the host-pathogen status and result in viral reactivation. These types of data will guide decision-making regarding the necessity of countermeasure development.
We addressed the mucosal immune system questions by using a ground-based mouse model (AOS of mice) and rotavirus (a gastroenteritis virus known to be a mucosal immunogen and to cause human disease). This model system does not simulate all aspects of space flight, but it is accepted as a model for studies on alterations of the immune system. Our results from the AOS mouse model suggest that alterations in mucosal immune responses do occur under simulated space flight conditions, but that neither a delay in rotavirus clearance nor possible alteration of IgG1 anamnestic antibody responses was critical for the resolution of primary rotavirus infection or protection from rotavirus challenge. However, our experiments do not exclude that other important alterations in the mucosal immune system may have occurred. We believe that an examination of more global changes in the mucosal immune system would provide a more thorough cataloging of the effects of AOS on the mucosal immune system.