1. Duane L. Pierson, Ph.D. NASA Johnson Space Center Houston, Texas Duane L. Pierson, Ph.D. NASA Johnson Space Center Houston, Texas

2. Muscle loss Fluid shifts, hematological changes Fluid shifts, hematological changes Neurosensory adaptations Gastrointestinal alterations Cardiovascular adaptations Taste and odor sensitivity Sleep and circadian rhythm disturbances Sleep and circadian rhythm disturbances Psychological-Behavioral- Performance issues Psychological-Behavioral- Performance issues Immune changes Bone loss ADAPTATION TO SPACEFLIGHT

3. HUMAN IMMUNE RESPONSE Blood Cell Count Blood Cell Count Lymphocyte Proliferative Responses Lymphocyte Proliferative Responses Cell Mediated Immunity Cell Mediated Immunity Cytokine Production Cytokine Production NK Cell Cytotoxicity NK Cell Cytotoxicity Humoral Factors Humoral Factors Specific Antibody Response Specific Antibody Response Wound Healing Wound Healing Neutrophil Functions Neutrophil Functions

4. HEALTH DISEASE Crowded Living Conditions Closed-Loop Environment (Water/Air) Reduced Capability for Personal Hygiene Limited Clean-up and Disinfection Capability Inability to Isolate Contagious Crewmember Limited Treatment Capability and Crew Return Altered Immune Response FACTORS INCREASING DISEASE RISK

5. Skin Infections Gastrointestinal Distress Urinary Tract Infections Upper Respiratory Latent Viral Reactivation INFECTIOUS DISEASE RISKS

6. SPECIFIC APPLICATION May be used as an early predictor of impending medically significant changes in the immune response. SPECIFIC APPLICATION May be used as an early predictor of impending medically significant changes in the immune response. uHerpesviruses are the most readily recognized latent viruses. uThese viruses are ubiquitous and represent important infectious disease risks with oncogenic potential. uHerpesviruses are the most readily recognized latent viruses. uThese viruses are ubiquitous and represent important infectious disease risks with oncogenic potential. WHY HERPESVIRUSES? uThey are not mitigated by preflight quarantine. uSpace flight stress alters immune response. uDiminished immunity results in reactivation and dissemination (“shedding”) of latent viruses. uThey are not mitigated by preflight quarantine. uSpace flight stress alters immune response. uDiminished immunity results in reactivation and dissemination (“shedding”) of latent viruses.

8. SALIVA COLLECTION PROCEDURE

10. Antarctica: EBV Days in Isolation EBV DNA O.D. @ 405nm DTH response -100-50050100150200250 0 1 2 3 4 5 Subject 1 Pre Normal Hypoergic Anergic Post Isolation

11. Space Shuttle: EBV copies EBV Copies per ml 0 200 400 600 800 1000 EBV Frequency: 29% EBV copies 40+ 2 Day before launch (L-) Day before launch (L-) 200-140139-6059-1 EBV Frequency:16% EBV copies 417+ 31 Day of flight Day of flight 2-45-78-14 Day after recovery (R+) Day after recovery (R+) 1-3031-45 EBV Frequency: 16% EBV copies 44+ 5 n = 32 Space Flights = 10 Control Mir

12. Space Shuttle: CMV Frequency % Positive CMV Urine Samples AstronautsControl 0 5 10 15 20 25 30 n = 71 n = 61

13. CMV IgG Antibody Titers (Mean +/- SE log 2 ) CMV IgG Antibody Titers (Mean +/- SE log 2 ) 55 Astronauts 40 non-shedders * significant increase from BL (p<0.001) † significant increase from L-10 (p< 0.001) BLL-10R+0R+3 2 3 4 5 6 7 8 15 CMV Shedders * * † *

16. CONCLUSIONS 1.Space flight is a unique stress model 2.Antarctic Science Stations model many aspects of space flight 3.Stress associated with space flight results in increased reactivation of EBV, CMV and VZV. 4.Viral reactivation in astronauts appears to be linked to duration in Space (Stress/ Microgravity ?). 5.Space flight associated stress manifested through the HPA-axis result in increased stress hormones, reduced CMI, and increased viral reactivation. 1.Space flight is a unique stress model 2.Antarctic Science Stations model many aspects of space flight 3.Stress associated with space flight results in increased reactivation of EBV, CMV and VZV. 4.Viral reactivation in astronauts appears to be linked to duration in Space (Stress/ Microgravity ?). 5.Space flight associated stress manifested through the HPA-axis result in increased stress hormones, reduced CMI, and increased viral reactivation.

17. Satish K Mehta, Ph.D., NASA-JSC Desmond J. Lugg, M.D., Australian Antarctic Div, Hobart, Australia Janet S. Butel, Ph.D., NSBRI/Baylor College of Medicine, Houston,TX Randall J. Cohrs, Ph.D., Uni Colorado Health Sciences Center, Denver Co Bagher Forghani, Ph.D.,California Department of Health Services, Richmond, CA Stephen K. Tyring, M.D., Ph.D., UTMB, Galveston, TX Ronald Glaser, Ph.D., The Ohio State University, Columbus, OH Satish K Mehta, Ph.D., NASA-JSC Desmond J. Lugg, M.D., Australian Antarctic Div, Hobart, Australia Janet S. Butel, Ph.D., NSBRI/Baylor College of Medicine, Houston,TX Randall J. Cohrs, Ph.D., Uni Colorado Health Sciences Center, Denver Co Bagher Forghani, Ph.D.,California Department of Health Services, Richmond, CA Stephen K. Tyring, M.D., Ph.D., UTMB, Galveston, TX Ronald Glaser, Ph.D., The Ohio State University, Columbus, OH ACKNOWLEDGEMENTS