The Impact of a 6-Month Mission to the International Space Station (ISS) on Salivary Antimicrobial Proteins and Latent Viral Reactivation: Exercise Training as a Potential Countermeasure



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As the international space community plans for manned missions to Mars, spaceflight associated immune dysregulation has been identified as a potential risk to the health and safety of the crew. Spaceflight has consistently been shown to dysregulate the normal functioning of the immune system including; latent viral reactivation, altered cytokine profiles, reduction in T-cell and NK-cell function. However, less is known about salivary antimicrobial proteins (sAMPs)- which act as a first line of innate immune defense against multiple pathogens. This dissertation sought to determine the effects of spaceflight on salivary markers of innate immunity and latent herpes virus reactivation. Additionally, suitable countermeasures are necessary to mitigate the space flight induced immune dysregulation. As moderate intensity exercise has consistently been shown to exert positive effects on the immune system, we determined whether pre-flight physical fitness, or its maintenance reduced the risk of viral reactivations. The aims of this dissertation were divided into three hypotheses: 1) Astronaut’s salivary immunity will be diminished during and immediately after spaceflight and they will encounter more latent viral reactivations than their ground based controls; 2a) Astronauts with higher fitness status will exhibit fewer incidences of viral reactivation compared to their lower fit counterparts; 2b) Astronauts who better maintain their fitness levels in flight will exhibit fewer incidences of viral reactivation compared to those who show greater physical fitness decline. To test Hypothesis 1 we collected saliva samples from 8 international space station (ISS) crewmembers and 7-ground-based controls pre-flight, mid-flight and post-flight. We measured several sAMPs by ELISA as well as detected shedding of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) DNA by RT-PCR. We found that salivary sIgA, lysozyme, LL-37, and the cortisol to DHEA ratio were elevated in the ISS crew before and during the mission. ‘Rookie’ crewmembers embarking on their first spaceflight mission had depressed levels of salivary sIgA but increased levels of α- amylase, lysozyme and LL-37 during and after the mission compared to the ‘veteran’ crew who had flown on a previous spaceflight mission. Crewmembers who shed a latent herpes virus during the mission had higher cortisol levels compared to those who did not shed. All salivary biomarkers remained unchanged in the ground-based controls. To test Hypothesis 2, we retrospectively analyzed scores on standardized tests of strength, muscular endurance, flexibility and aerobic fitness (V ̇O2Max) in 22 ISS crewmembers before launch and after a ~6-month mission. The incidences and severity of CMV, EBV and VZV were also determined. We found that crewmembers with higher levels of aerobic fitness [American College of Sports Medicine (ACSM) classification of ‘superior’ or ‘excellent’] prior to the mission had a 31% reduced risk of latent viral reactivation compared to their lower ranked counterparts. We also found that higher levels of pre-flight upper body muscular endurance was associated with a 39% lower risk of latent viral reactivation. Crewmembers who better maintained V ̇O2Max scores after returning from the ISS tended to have a lower incidence of a viral reactivation. All crewmembers in the lower pre-flight aerobic fitness category who also demonstrated higher losses in V ̇O2Max reactivated all latent viruses. From the results of this dissertation, we conclude that long duration spaceflight alters the concentration and/or secretion of several sAMPs, some of which are related to crewmember flight experience, biomarkers of stress and latent viral reactivation. Additionally, we found that a pre-flight V ̇O2max score above the 80th percentile for age and sex, maintaining aerobic capacity during flight, and/or having above average scores of upper-body muscular endurance, may protect against latent viral reactivation during long duration space travel.



Latent viral reactivation, Immunology, Astronauts, Spaceflight, Herpesvirus, Countermeasures