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Project Title:  Space Flight-Induced Reactivation of Latent Epstein-Barr Virus Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2004  
End Date: 06/30/2010  
Task Last Updated: 10/15/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stowe, Raymond  Ph.D. / Microgen  
Address:  903 Texas Avenue 
 
La Marque , TX 77568-3318 
Email: rpstowe@microgenlabs.com, brian.crucian-1@nasa.gov 
Phone: 409-935-6700  
Congressional District: 22 
Web:  
Organization Type: INDUSTRY 
Organization Name: Microgen  
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pierson, Duane L  NASA Johnson Space Center 
Sams, Clarence  NASA-Johnson Space Center 
Key Personnel Changes / Previous PI: Raymond Stowe replaced Alan Barrett as PI, effective July 2004 (per info from S. McCollum/M. Anderson, 12/2006). See also Barrett for FY02-04 information/reports.
Project Information: Grant/Contract No. NNJ06HB73A 
Responsible Center: NASA JSC 
Grant Monitor: Meck, J@n  
Center Contact: 281-244-5405 
janice.v.meck@nasa.gov 
Solicitation / Funding Source: 98-HEDS-02 
Grant/Contract No.: NNJ06HB73A 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM02:It is necessary to define a flight standard related to spaceflight-associated immune system dysregulation (IRP Rev E)
(3) IM05:What is the time course and etiology of immune changes? (MERGED with IM1, per IRP Rev E)
Flight Assignment/Project Notes: STS-122, STS-123, STS-124, STS-125, STS-126

STS-108, -109, -110, -111, -113, -114; -116; -118;

ISS-5, -6, -11, 12, -13, -14, -15, and -16

In flight development phase (data collection has begun)

NOTE: End date is 6/30/2010 per JSC information (2/2010)

NOTE: End date changed to 1/22/2010 per J. Dardano/JSC (1/2009)

Task Description: The majority of humans are infected with Epstein-Barr virus (EBV) early in life and thereafter carry the virus in a latent form. Reactivation of latent EBV may be an important threat to crew health during extended space missions. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and different kinds of B-lymphocyte lymphomas in immunosuppressed individuals. Control of replication in vivo is mediated primarily by EBV- specific cytotoxic T-lymphocytes, and severe clinical symptoms have been associated with reactivation of latent viruses in patients with defective cellular immunity. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. Based on these observations, we hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B- lymphocytes. The specific aims to test this hypothesis are: (1) determine if antibody titers to EBV-specific antigens are increased after space flight; (2) determine T-lymphocyte immunocompetence using a EBV-specific autologous T-cell killing assay; (3) characterize the viral burden and gene expression in peripheral blood cells using PCR/RT-PCR; and (4) measure stress hormones in plasma and urine.

To determine the mechanisms underlying altered virus-specific T cell immunity and reactivation of latent EBV in B lymphocytes.

See also http://www.nasa.gov/mission_pages/station/science/experiments/Epstein-Barr.html

Research Impact/Earth Benefits: This experiment will address fundamental questions on spaceflight and virus-specific immunity. One potential concern is the development of a virally associated disease or lymphoma within an infected individual. In addition, reinfection or transmission to a previously uninfected individual (resulting in primary infection) may be another concern. Thus, spaceflight may result in an increased frequency and/or severity of both primary and reactivated disease. If increased reactivation and clonal expansion of infected B- lymphocytes is detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease.

Task Progress & Bibliography Information FY2010 
Task Progress: Eight separate samples of peripheral blood were collected from each of 63 astronauts; 45 flew on fourteen Space Shuttle missions (39 men, 6 women, mean age 46 ± 5) and 18 flew on eight ISS missions (15 men, 3 women, mean age 48 ± 4); the average length of the Shuttle missions was ~11 days while the average length of the ISS missions was ~180 days. Space Shuttle missions included STS-108, -109, -110, -111, -113, 114, -115, -116, -118, -121, -123, -124, -125, and -126. ISS missions included ISS-5, -6, -11, 12, -13, -14, -15, and -16. Peripheral blood was collected 180 days before launch (L-180), L-65-44, L-10, L-2, within 4 h after return/landing (R+0), R+3, R+14-30, and R+180.

We analyzed blood and urine samples for: 1) stress hormone levels; 2) general and virus-specific immunity; and 3) latent herpesvirus reactivation. Our data showed that stress- and space flight-associated changes (e.g., anticipation of launch, acute changes in g-forces, sleep deprivation, etc.) resulted in a decline in cellular immunity and an increase in viral reactivation. We propose that the accumulative effects of microgravity (i.e., muscle loss and generalized physiological deconditioning) associated with longer duration missions resulted in increased sympathetic nervous system activation and increased hypothalamic pituitary adrenal axis activation at landing. This would be a possible explanation for the differences observed in results from the ISS crewmembers versus those from Shuttle crewmembers. This data also further supports our hypothesis that a Th1-to-Th2 shift in cytokine production may be partially responsible for many of the immune alterations in astronauts.

Bibliography Type: Description: (Last Updated: 03/07/2019)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Crucian B, Stowe R, Mehta S, Uchakin P, Quiriarte H, Pierson D, Sams C. "Validation of Procedures for Monitoring Crewmember Immune Function." NASA Human Research Program Investigators’ Workshop, League City, TX, February 2009.

Program and abstracts. http://www.dsls.usra.edu/meetings/hrp2010/pdf/Immunology/1151CrucianMehta-IntImm.pdf , Feb-2010 , Feb-2009

Abstracts for Journals and Proceedings Stowe RP, Komanduri K, St. John LS, Sams CF, Pierson DL. "Spaceflight and aging: Immune system parallels." NASA Human Research Program Investigators’ Workshop, League City, TX, February 2009.

Program and abstracts: http://www.dsls.usra.edu/meetings/hrp2009/pdf/Immune/1114Stowe.pdf , Feb-2009

Articles in Peer-reviewed Journals Stowe RP, Kozlova EV, Sams CF, Pierson DL, Walling DM. "Latent and lytic Epstein-Barr virus gene expression in the peripheral blood of astronauts." J Med Virol. 2011 Jun;83(6):1071-7. http://dx.doi.org/10.1002/jmv.22079 ; PubMed PMID: 21503923 , Jun-2011
Articles in Peer-reviewed Journals Stowe RP, Sams CF, Pierson DL. "Adrenocortical and immune responses following short- and long-duration spaceflight." Aviat Space Environ Med. 2011 Jun;82(6):627-34. PubMed PMID: 21702314 , Jun-2011
Articles in Peer-reviewed Journals Crucian B, Stowe R, Quiriarte H, Pierson D, Sams C. "Monocyte phenotype and cytokine production profiles are dysregulated by short-duration spaceflight." Aviat Space Environ Med. 2011 Sep;82(9):857-62. PubMed PMID: 21888268 , Sep-2011
Articles in Peer-reviewed Journals Stowe RP, Ruiz RJ, Fagundes CP, Stowe RH, Chen M, Glaser R. "An ELISA method to compute endpoint titers to Epstein-Barr virus and cytomegalovirus: application to population-based studies." J Immunol Methods. 2014 Jun;408:64-9. http://dx.doi.org/10.1016/j.jim.2014.05.006 ; PubMed PMID: 24859346; PubMed Central PMCID: PMC4098116 , Jun-2014
Articles in Peer-reviewed Journals Benjamin CL, Stowe RP, St John L, Sams CF, Mehta SK, Crucian BE, Pierson DL, Komanduri KV. "Decreases in thymopoiesis of astronauts returning from space flight." JCI Insight. 2016 Aug 4;1(12):e88787. https://doi.org/10.1172/jci.insight.88787 ; PubMed PMID: 27699228 ; PubMed Central PMCID: PMC5033888 , Aug-2016
Books/Book Chapters Stowe RP, Goodwin JS. "Effects of aging on immune function." in "Principles and Practice of Geriatric Surgery. 2nd edition." Ed. R.A. Rosenthal, M.E. Zenilman, M.R. Katlic. New York : Springer, 2011. p. 46-64., Jul-2011
Project Title:  Space Flight-Induced Reactivation of Latent Epstein-Barr Virus Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2004  
End Date: 06/30/2010  
Task Last Updated: 03/25/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stowe, Raymond  Ph.D. / Microgen  
Address:  903 Texas Avenue 
 
La Marque , TX 77568-3318 
Email: rpstowe@microgenlabs.com, brian.crucian-1@nasa.gov 
Phone: 409-935-6700  
Congressional District: 22 
Web:  
Organization Type: INDUSTRY 
Organization Name: Microgen  
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pierson, Duane L  NASA Johnson Space Center 
Sams, Clarence  NASA-Johnson Space Center 
Key Personnel Changes / Previous PI: Raymond Stowe replaced Alan Barrett as PI, effective July 2004 (per info from S. McCollum/M. Anderson, 12/2006). See also Barrett for FY02-04 information/reports.
Project Information: Grant/Contract No. NNJ06HB73A 
Responsible Center: NASA JSC 
Grant Monitor: Meck, J@n  
Center Contact: 281-244-5405 
janice.v.meck@nasa.gov 
Solicitation / Funding Source: 98-HEDS-02 
Grant/Contract No.: NNJ06HB73A 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM02:It is necessary to define a flight standard related to spaceflight-associated immune system dysregulation (IRP Rev E)
(3) IM05:What is the time course and etiology of immune changes? (MERGED with IM1, per IRP Rev E)
Flight Assignment/Project Notes: STS-122, STS-123, STS-124, and STS-125

STS-108, -109, -110, -111, -113, -114; -116; -118;

ISS-5, -6

In flight development phase (data collection has begun)

NOTE: End date is 6/30/2010 per JSC information (2/2010)

NOTE: End date changed to 1/22/2010 per J. Dardano/JSC (1/2009)

Task Description: The majority of humans are infected with Epstein-Barr virus (EBV) early in life and thereafter carry the virus in a latent form. Reactivation of latent EBV may be an important threat to crew health during extended space missions. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and different kinds of B-lymphocyte lymphomas in immunosuppressed individuals. Control of replication in vivo is mediated primarily by EBV- specific cytotoxic T-lymphocytes, and severe clinical symptoms have been associated with reactivation of latent viruses in patients with defective cellular immunity. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. Based on these observations, we hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B- lymphocytes. The specific aims to test this hypothesis are: (1) determine if antibody titers to EBV-specific antigens are increased after space flight; (2) determine T-lymphocyte immunocompetence using a EBV-specific autologous T-cell killing assay; (3) characterize the viral burden and gene expression in peripheral blood cells using PCR/RT-PCR; and (4) measure stress hormones in plasma and urine.

To determine the mechanisms underlying altered virus-specific T cell immunity and reactivation of latent EBV in B lymphocytes.

See also http://www.nasa.gov/mission_pages/station/science/experiments/Epstein-Barr.html

Research Impact/Earth Benefits: This experiment will address fundamental questions on spaceflight and virus-specific immunity. One potential concern is the development of a virally associated disease or lymphoma within an infected individual. In addition, reinfection or transmission to a previously uninfected individual (resulting in primary infection) may be another concern. Thus, spaceflight may result in an increased frequency and/or severity of both primary and reactivated disease. If increased reactivation and clonal expansion of infected B- lymphocytes is detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease.

Task Progress & Bibliography Information FY2009 
Task Progress: Since our last task progress report, we have collected samples from an additional 6 Shuttle and 2 ISS crewmembers. We are continuing to observe elevated cortisol levels at landing; the increase is typically more exaggerated for ISS crewmembers. Along with this are increased levels of epinephrine postflight. The typical stress-induced shifts in leukocytes (neutrophilia) and lymphocytes (lymphopenia, decreased NK cells), observed after spaceflight, are consistent with increased stress hormone levels. Many of the astronauts exhibited increased levels of EBV-specific CD8+ T-cells prior to flight, consistent with increased viral reactivation as determined by increased viral load and increased anti-EBV antibodies. In some astronauts, increased levels of IL-10 were observed indicating a Th1-Th2 shift in immunity. In addition, increased IL-6 (a proinflammatory cytokine) was observed in a few crewmembers.

Overall, these results are consistent with prior missions and indicate that stress and spaceflight-associated changes (e.g., anticipation of launch, acute changes in g-forces, sleep deprivation, etc.) result in decreased cell-mediated immunity and reactivation of latent EBV. Furthermore, changes in immunity occur prior to launch, presumably due to anticipation of the mission. Therefore, employing interventions (stress reduction, exercise, etc.) in the months prior to launch would be an effective means to counter the effects of spaceflight on the immune system.

Bibliography Type: Description: (Last Updated: 03/07/2019)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Crucian BE, Stowe RP, Pierson DL, Sams CF. "Immune system dysregulation following short- vs long-duration spaceflight." Aviat Space Environ Med. 2008 Sep;79(9):835-43. PMID: 18785351 , Sep-2008
Project Title:  Space Flight-Induced Reactivation of Latent Epstein-Barr Virus Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2004  
End Date: 01/22/2010  
Task Last Updated: 05/05/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stowe, Raymond  Ph.D. / Microgen  
Address:  903 Texas Avenue 
 
La Marque , TX 77568-3318 
Email: rpstowe@microgenlabs.com, brian.crucian-1@nasa.gov 
Phone: 409-935-6700  
Congressional District: 22 
Web:  
Organization Type: INDUSTRY 
Organization Name: Microgen  
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pierson, Duane L  NASA Johnson Space Center 
Key Personnel Changes / Previous PI: Raymond Stowe replaced Alan Barrett as PI, effective July 2004 (per info from S. McCollum/M. Anderson, 12/2006). See also Barrett for FY02-04 information/reports.
Project Information: Grant/Contract No. NNJ06HB73A 
Responsible Center: NASA JSC 
Grant Monitor: Meck, J@n  
Center Contact: 281-244-5405 
janice.v.meck@nasa.gov 
Solicitation / Funding Source: 98-HEDS-02 
Grant/Contract No.: NNJ06HB73A 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM02:It is necessary to define a flight standard related to spaceflight-associated immune system dysregulation (IRP Rev E)
(3) IM05:What is the time course and etiology of immune changes? (MERGED with IM1, per IRP Rev E)
Flight Assignment/Project Notes: STS-122, STS-123, STS-124, and STS-125

STS-108, -109, -110, -111, -113, -114; -116; -118;

ISS-5, -6

In flight development phase (data collection has begun)

NOTE: End date changed to 1/22/2010 per J. Dardano/JSC (1/2009)

Task Description: The majority of humans are infected with Epstein-Barr virus (EBV) early in life and thereafter carry the virus in a latent form. Reactivation of latent EBV may be an important threat to crew health during extended space missions. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and different kinds of B-lymphocyte lymphomas in immunosuppressed individuals. Control of replication in vivo is mediated primarily by EBV- specific cytotoxic T-lymphocytes, and severe clinical symptoms have been associated with reactivation of latent viruses in patients with defective cellular immunity. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. Based on these observations, we hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B- lymphocytes. The specific aims to test this hypothesis are: (1) determine if antibody titers to EBV-specific antigens are increased after space flight; (2) determine T-lymphocyte immunocompetence using a EBV-specific autologous T-cell killing assay; (3) characterize the viral burden and gene expression in peripheral blood cells using PCR/RT-PCR; and (4) measure stress hormones in plasma and urine.

To determine the mechanisms underlying altered virus-specific T cell immunity and reactivation of latent EBV in B lymphocytes.

See also http://www.nasa.gov/mission_pages/station/science/experiments/Epstein-Barr.html

Research Impact/Earth Benefits: This experiment will address fundamental questions on spaceflight and virus-specific immunity. One potential concern is the development of a virally associated disease or lymphoma within an infected individual. In addition, reinfection or transmission to a previously uninfected individual (resulting in primary infection) may be another concern. Thus, spaceflight may result in an increased frequency and/or severity of both primary and reactivated disease. If increased reactivation and clonal expansion of infected B- lymphocytes is detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease.

Task Progress & Bibliography Information FY2008 
Task Progress: Our experiment has been manifested on several more Shuttle missions including STS-122, STS-123, STS-124, and STS-125. Completed missions included STS-116 and STS-118. We have also enrolled subjects from STS-126.

Bibliography Type: Description: (Last Updated: 03/07/2019)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Stowe RP, Sams CF, Pierson DL. "Cytomegalovirus reactivation in astronauts." NASA Human Research Program Investigators’ Workshop, League City, TX, January 2008.

NASA Human Research Program Investigators’ Workshop Proceedings, January 2008. , Jan-2008

Abstracts for Journals and Proceedings Crucian B, Stowe R, Mehta S, Uchakin P, Quiriarte H, Pierson D, Sams C. "Validation of Procedures for Monitoring Crewmember Immune Function." NASA Human Research Program Investigators’ Workshop, League City, TX, January 2008.

NASA Human Research Program Investigators’ Workshop Proceedings, January 2008. , Jan-2008

Abstracts for Journals and Proceedings Crucian B, Stowe R, Mehta S, Uchakin P, Quiriarte H, Yetman D, Pierson D, Sams C. "Immune function changes during a spaceflight-analog undersea mission." NASA Human Research Program Investigators’ Workshop, League City, TX, January 2008.

NASA Human Research Program Investigators’ Workshop Proceedings, January 2008. , Jan-2008

Abstracts for Journals and Proceedings Mehta SK, Aggarwal BB, Feiveson AH, Hammond DK, Castro VA, Stowe RP, Pierson DL. "Plasma cytokine levels in astronauts before and after spaceflight." NASA Human Research Program Investigators’ Workshop, League City, TX, January 2008.

NASA Human Research Program Investigators’ Workshop Proceedings, January 2008. , Jan-2008

Articles in Peer-reviewed Journals Stowe RP, Kozlova EV, Yetman DL, Walling DM, Goodwin JS, Glaser R. "Chronic herpesvirus reactivation occurs in aging. " Exp Gerontol. 2007 Jun;42(6):563-70. Epub 2007 Jan 30. PMID: 17337145 , Jun-2007
Articles in Peer-reviewed Journals Uchakin PN, Stowe RP, Paddon-Jones D, Tobin BW, Ferrando AA, Wolfe RR. "Cytokine secretion and latent herpes virus reactivation with 28 days of horizontal hypokinesia." Aviat Space Environ Med. 2007 Jun;78(6):608-12. PMID: 17571663 , Jun-2007
Articles in Peer-reviewed Journals Mehta SK, Crucian B, Pierson DL, Sams C, Stowe RP. "Monitoring immune system function and reactivation of latent viruses in the Artificial Gravity Pilot Study." J Gravit Physiol. 2007 Jul;14(1):P21-5. PMID: 18372687 , Jul-2007
Articles in Peer-reviewed Journals Stowe RP, Yetman DL, Storm WF, Sams CF, Pierson DL. "Neuroendocrine and immune responses to 16-day bed rest with realistic launch and landing G profiles." Aviat Space Environ Med. 2008 Feb;79(2):117-22. PMID: 18309909 , Feb-2008
Articles in Peer-reviewed Journals Crucian B, Lee P, Stowe R, Jones J, Effenhauser R, Widen R, Sams C. "Immune system changes during simulated planetary exploration on Devon Island, high arctic." BMC Immunol. 2007 May 23;8:7. PMID: 17521440 , May-2007
Project Title:  Space Flight-Induced Reactivation of Latent Epstein-Barr Virus Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2004  
End Date: 12/31/2008  
Task Last Updated: 04/25/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stowe, Raymond  Ph.D. / Microgen  
Address:  903 Texas Avenue 
 
La Marque , TX 77568-3318 
Email: rpstowe@microgenlabs.com, brian.crucian-1@nasa.gov 
Phone: 409-935-6700  
Congressional District: 22 
Web:  
Organization Type: INDUSTRY 
Organization Name: Microgen  
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pierson, Duane L  NASA Johnson Space Center 
Key Personnel Changes / Previous PI: Raymond Stowe replaced Alan Barrett as PI, effective July 2004 (per info from S. McCollum/M. Anderson, 12/2006). See also Barrett for FY02-04 information/reports.
Project Information: Grant/Contract No. NNJ06HB73A 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: 98-HEDS-02 
Grant/Contract No.: NNJ06HB73A 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM02:It is necessary to define a flight standard related to spaceflight-associated immune system dysregulation (IRP Rev E)
(3) IM05:What is the time course and etiology of immune changes? (MERGED with IM1, per IRP Rev E)
Flight Assignment/Project Notes: STS-108, -109, -110, -111, -113, -114; ISS-5, -6 In flight development phase (data collection has begun)

Task Description: The majority of humans are infected with Epstein-Barr virus (EBV) early in life and thereafter carry the virus in a latent form. Reactivation of latent EBV may be an important threat to crew health during extended space missions. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and different kinds of B-lymphocyte lymphomas in immunosuppressed individuals. Control of replication in vivo is mediated primarily by EBV- specific cytotoxic T-lymphocytes, and severe clinical symptoms have been associated with reactivation of latent viruses in patients with defective cellular immunity. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. Based on these observations, we hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B- lymphocytes. The specific aims to test this hypothesis are: (1) determine if antibody titers to EBV-specific antigens are increased after space flight; (2) determine T-lymphocyte immunocompetence using a EBV-specific autologous T-cell killing assay; (3) characterize the viral burden and gene expression in peripheral blood cells using PCR/RT-PCR; and (4) measure stress hormones in plasma and urine.

To determine the mechanisms underlying altered virus-specific T cell immunity and reactivation of latent EBV in B lymphocytes.

Research Impact/Earth Benefits: This experiment will address fundamental questions on spaceflight and virus-specific immunity. One potential concern is the development of a virally associated disease or lymphoma within an infected individual. In addition, reinfection or transmission to a previously uninfected individual (resulting in primary infection) may be another concern. Thus, spaceflight may result in an increased frequency and/or severity of both primary and reactivated disease. If increased reactivation and clonal expansion of infected B- lymphocytes is detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease.

Task Progress & Bibliography Information FY2007 
Task Progress: Since our last task progress report, we have collected samples from an additional 14 Shuttle crewmembers and 7 ISS crewmembers. Multiple pre- and post-flight samples were collected in this study to better characterize changes in neuroendocrine hormones, immune function, and latent herpesvirus reactivation. We measured plasma and urinary stress hormones, and intracellular cytokine production by antigen-specific T cells. In addition, we performed nested RT-PCR on isolated B-cells to determine the EBV gene expression pattern before and after space flight.

Our results demonstrate that mission duration significantly affects neuroimmune responses and latent EBV reactivation. Elevated levels of cortisol were found in blood and urine after landing for Shuttle crewmembers. For ISS crewmembers, cortisol was significantly higher at landing and 3-5 times higher than levels found for Shuttle crewmembers. Production of intracellular tumor necrosis factor-alpha and interferon-gamma by SEB-stimulated CD4+ T cells were decreased just before launch as compared to baseline levels indicating a generalized stress-induced decrease in immune function. Cytokine production was also decreased immediately after space flight. EBV gene expression, grouped according to latent, immediate early/early (IE/E), and late replicative transcription (LR), was assessed in blood samples taken from healthy young and elderly subjects to compare with data from the Shuttle and ISS astronaut samples. In samples from younger control subjects (n=24), EBV gene expression was highly restricted (5 samples positive for latent genes, 3 samples positive for IE/E, no samples positive for LR). EBV gene expression in samples from elderly subjects displayed frequent transcription of latent and LR genes that was indicative of chronic EBV reactivation. In Shuttle astronaut samples, EBV gene expression shifted towards the IE/E expression. Notably, for ISS crewmembers there were increases in both latent and IE/E transcripts. Furthermore, LR transcripts (BALF5 and gp220) were present in samples collected immediately after landing but not before flight. The pattern of EBV gene transcription from ISS astronauts was similar to that found in aging samples. Overall, these results indicate that stress and spaceflight-associated changes (e.g., anticipation of launch, acute changes in g-forces, sleep deprivation, etc.) resulted in decreased cell-mediated immunity and reactivation of latent EBV in both Shuttle and ISS crewmembers.

Bibliography Type: Description: (Last Updated: 03/07/2019)  Show Cumulative Bibliography Listing
 
Books/Book Chapters Pierson DL, Mehta SK, Stowe RP. "Reactivation of Latent Herpes Viruses in Astronauts." in "Psychoneuroimmunology, Fourth Edition." Ed. R. Ader. Boston : Academic Press , p. 851-868, 2007., Jan-2007
Project Title:  Space Flight-Induced Reactivation of Latent Epstein-Barr Virus Reduce
Fiscal Year: FY 2006 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2004  
End Date: 12/31/2008  
Task Last Updated: 04/25/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stowe, Raymond  Ph.D. / Microgen  
Address:  903 Texas Avenue 
 
La Marque , TX 77568-3318 
Email: rpstowe@microgenlabs.com, brian.crucian-1@nasa.gov 
Phone: 409-935-6700  
Congressional District: 22 
Web:  
Organization Type: INDUSTRY 
Organization Name: Microgen  
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pierson, Duane L  NASA Johnson Space Center 
Key Personnel Changes / Previous PI: Raymond Stowe replaced Alan Barrett as PI, effective July 2004 (per info from S. McCollum/M. Anderson, 12/2006). See also Barrett for FY02-04 information/reports.
Project Information: Grant/Contract No. NNJ06HB73A 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: 98-HEDS-02 
Grant/Contract No.: NNJ06HB73A 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM02:It is necessary to define a flight standard related to spaceflight-associated immune system dysregulation (IRP Rev E)
(3) IM05:What is the time course and etiology of immune changes? (MERGED with IM1, per IRP Rev E)
Flight Assignment/Project Notes: STS-108, -109, -110, -111, -113, -114; ISS-5, -6 In flight development phase (data collection has begun)

Task Description: The majority of humans are infected with Epstein-Barr virus (EBV) early in life and thereafter carry the virus in a latent form. Reactivation of latent EBV may be an important threat to crew health during extended space missions. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and different kinds of B-lymphocyte lymphomas in immunosuppressed individuals. Control of replication in vivo is mediated primarily by EBV- specific cytotoxic T-lymphocytes, and severe clinical symptoms have been associated with reactivation of latent viruses in patients with defective cellular immunity. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. Based on these observations, we hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B- lymphocytes. The specific aims to test this hypothesis are: (1) determine if antibody titers to EBV-specific antigens are increased after space flight; (2) determine T-lymphocyte immunocompetence using a EBV-specific autologous T-cell killing assay; (3) characterize the viral burden and gene expression in peripheral blood cells using PCR/RT-PCR; and (4) measure stress hormones in plasma and urine.

To determine the mechanisms underlying altered virus-specific T cell immunity and reactivation of latent EBV in B lymphocytes.

Research Impact/Earth Benefits: This experiment will address fundamental questions on spaceflight and virus-specific immunity. One potential concern is the development of a virally associated disease or lymphoma within an infected individual. In addition, reinfection or transmission to a previously uninfected individual (resulting in primary infection) may be another concern. Thus, spaceflight may result in an increased frequency and/or severity of both primary and reactivated disease. If increased reactivation and clonal expansion of infected B- lymphocytes is detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease.

Task Progress & Bibliography Information FY2006 
Task Progress: See FY2007 report.

Bibliography Type: Description: (Last Updated: 03/07/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2006
Project Title:  Space Flight-Induced Reactivation of Latent Epstein-Barr Virus Reduce
Fiscal Year: FY 2005 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2004  
End Date: 12/31/2008  
Task Last Updated: 01/22/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stowe, Raymond  Ph.D. / Microgen  
Address:  903 Texas Avenue 
 
La Marque , TX 77568-3318 
Email: rpstowe@microgenlabs.com, brian.crucian-1@nasa.gov 
Phone: 409-935-6700  
Congressional District: 22 
Web:  
Organization Type: INDUSTRY 
Organization Name: Microgen  
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pierson, Duane L  NASA Johnson Space Center  
Key Personnel Changes / Previous PI: Raymond Stowe replaced Alan Barrett as PI, effective July 2004 (per info from S. McCollum/M. Anderson, 12/2006). See also Barrett for FY02-04 information/reports.
Project Information: Grant/Contract No. NNJ06HB73A 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: 98-HEDS-02 
Grant/Contract No.: NNJ06HB73A 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM02:It is necessary to define a flight standard related to spaceflight-associated immune system dysregulation (IRP Rev E)
(3) IM05:What is the time course and etiology of immune changes? (MERGED with IM1, per IRP Rev E)
Flight Assignment/Project Notes: STS-108, -109, -110, -111, -113, -114; ISS-5, -6 In flight development phase (data collection has begun)

Task Description: The majority of humans are infected with Epstein-Barr virus (EBV) early in life and thereafter carry the virus in a latent form. Reactivation of latent EBV may be an important threat to crew health during extended space missions. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and different kinds of B-lymphocyte lymphomas in immunosuppressed individuals. Control of replication in vivo is mediated primarily by EBV- specific cytotoxic T-lymphocytes, and severe clinical symptoms have been associated with reactivation of latent viruses in patients with defective cellular immunity. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. Based on these observations, we hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B- lymphocytes. The specific aims to test this hypothesis are: (1) determine if antibody titers to EBV-specific antigens are increased after space flight; (2) determine T-lymphocyte immunocompetence using a EBV-specific autologous T-cell killing assay; (3) characterize the viral burden and gene expression in peripheral blood cells using PCR/RT-PCR; and (4) measure stress hormones in plasma and urine.

To determine the mechanisms underlying altered virus-specific T cell immunity and reactivation of latent EBV in B lymphocytes.

Research Impact/Earth Benefits: This experiment will address fundamental questions on spaceflight and virus-specific immunity. One potential concern is the development of a virally associated disease or lymphoma within an infected individual. In addition, reinfection or transmission to a previously uninfected individual (resulting in primary infection) may be another concern. Thus, spaceflight may result in an increased frequency and/or severity of both primary and reactivated disease. If increased reactivation and clonal expansion of infected B- lymphocytes is detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease.

Task Progress & Bibliography Information FY2005 
Task Progress: Multiple pre- and post-flight samples were collected in this study to better characterize changes in neuroendocrine hormones, immune function, and latent herpesvirus reactivation. To date, we have collected longitudinal samples from six International Space Station crewmembers from Expeditions 5 and 6; the duration was 184 days and 161 days, respectively. We measured plasma and urinary cortisol, plasma cytokines (IL-6, -10), intracellular cytokine production by antigen-specific T cells, and viral load in peripheral blood. Elevated levels of cortisol were found in blood and urine after landing. Altered levels of IL-6 and IL-10 were also observed. Production of intracellular tumor necrosis factor-alpha and interferon-gamma by CD4+ T cells were decreased just before launch as compared to baseline levels indicating a generalized stress-induced decrease in immune function. Cytokine production was also decreased immediately after space flight and returned to baseline levels within a few days after landing. Notably, viral load was higher in peripheral blood collected at landing as compared to preflight levels suggesting an expansion of virally-infected lymphocytes during flight. Collectively, these preliminary data indicate that stress- and space flight-associated changes (e.g., anticipation of launch, acute changes in g-forces, sleep deprivation, etc.) resulted in a decline in cellular immunity and an increase in viral load after space flight.

Our next ISS experiment will begin with Expedition 11, and our next Shuttle mission will begin with STS-114.

Bibliography Type: Description: (Last Updated: 03/07/2019)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Pierson DL, Stowe RP, Phillips TM, Lugg DJ, Mehta SK. "Epstein-Barr virus shedding by astronauts during space flight." Brain Behav Immun. 2005 May;19(3):235-42. PMID: 15797312 , May-2005
Project Title:  Space Flight-Induced Reactivation of Latent Epstein-Barr Virus Reduce
Fiscal Year: FY 2004 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2004  
End Date: 12/31/2008  
Task Last Updated: 01/06/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stowe, Raymond  Ph.D. / Microgen  
Address:  903 Texas Avenue 
 
La Marque , TX 77568-3318 
Email: rpstowe@microgenlabs.com, brian.crucian-1@nasa.gov 
Phone: 409-935-6700  
Congressional District: 22 
Web:  
Organization Type: INDUSTRY 
Organization Name: Microgen  
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pierson, Duane L  NASA Johnson Space Center 
Key Personnel Changes / Previous PI: Raymond Stowe replaced Alan Barrett as PI, effective July 2004 (per info from S. McCollum/M. Anderson, 12/2006). See also Barrett for FY02-04 information/reports.
Project Information: Grant/Contract No. NNJ06HB73A 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: 98-HEDS-02 
Grant/Contract No.: NNJ06HB73A 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM01:We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months (IRP Rev E)
(2) IM02:It is necessary to define a flight standard related to spaceflight-associated immune system dysregulation (IRP Rev E)
(3) IM05:What is the time course and etiology of immune changes? (MERGED with IM1, per IRP Rev E)
Flight Assignment/Project Notes: STS-108, -109, -110, -111, -113, -114;

ISS-5, -6 In flight development phase (data collection has begun)

Task Description: The majority of humans are infected with Epstein-Barr virus (EBV) early in life and thereafter carry the virus in a latent form. Reactivation of latent EBV may be an important threat to crew health during extended space missions. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and different kinds of B-lymphocyte lymphomas in immunosuppressed individuals. Control of replication in vivo is mediated primarily by EBV- specific cytotoxic T-lymphocytes, and severe clinical symptoms have been associated with reactivation of latent viruses in patients with defective cellular immunity. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. Based on these observations, we hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B- lymphocytes. The specific aims to test this hypothesis are: (1) determine if antibody titers to EBV-specific antigens are increased after space flight; (2) determine T-lymphocyte immunocompetence using a EBV-specific autologous T-cell killing assay; (3) characterize the viral burden and gene expression in peripheral blood cells using PCR/RT-PCR; and (4) measure stress hormones in plasma and urine.

To determine the mechanisms underlying altered virus-specific T cell immunity and reactivation of latent EBV in B lymphocytes.

See also http://www.nasa.gov/mission_pages/station/science/experiments/Epstein-Barr.html

Research Impact/Earth Benefits: This experiment will address fundamental questions on spaceflight and virus-specific immunity. One potential concern is the development of a virally associated disease or lymphoma within an infected individual. In addition, reinfection or transmission to a previously uninfected individual (resulting in primary infection) may be another concern. Thus, spaceflight may result in an increased frequency and/or severity of both primary and reactivated disease. If increased reactivation and clonal expansion of infected B- lymphocytes is detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease.

Task Progress & Bibliography Information FY2004 
Task Progress: Raymond Stowe replaced Alan Barrett as PI, effective July 2004 (per info from S. McCollum/M. Anderson, 12/2006). See also Barrett for FY02-04 information/reports.

[Ed. note: FY2004 record added to Task Book Jan 2010 for statistical purposes]

Bibliography Type: Description: (Last Updated: 03/07/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2004