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Monitoring Latent Virus Reactivation and Shedding in Astronauts (DSO 493)

Latent virus reactivation may be an important threat to crew health during extended space missions as crewmembers live and work in a closed environment. Infectious disease risks associated with latent viruses are not mitigated by a quarantine period before space flight or by prophylactic treatment, as are most bacterial, fungal, viral, and parasitic agents. Herpesviruses are the most readily recognized of the latent viruses and are the leading infectious cause of blindness in the United States. The establishment of latency and the subsequent reactivation are not well understood, but decrements in the immune system are known to increase the incidence and duration of viral reactivation and shedding of some latent viruses. An increasing body of evidence indicates that the physical and psychological stressors associated with space flight cause anomalies in the human immune response.

There are eight known human herpes viruses, and they are the most widely known latent viruses in humans. These viruses may be asymptomatic upon first exposure or cause a variety of primary diseases ranging from a sore throat to chickenpox. As the primary infection begins to subside, the viruses become latent in a variety of body tissues. Then during periods of decreased immunity, these viruses can reactivate, proliferate, and cause disease. Three of the eight human herpes viruses were routinely monitored in this study: 1) Epstein-Barr virus (EBV), 2) Cytomegalovirus (CMV), and 3) Varicella zoster (VZV). The primary technology used to detect and measure the extent of viral reactivation was the polymerase chain reaction (PCR). This molecular technology is sensitive, specific, and rapid. Viral plaque formation in tissue culture is the traditional method, but it is slow and some of the herpes viruses are difficult to culture. Culturing for viruses was used late in the study to demonstrate viable viruses. A detailed description of each virus studied is given below.

Epstein-Barr virus (EBV): EBV becomes latent in B-cells and perhaps some other tissues. When it reactivates, it can cause infectious mononucleosis in young adults. In severe immuno-suppressed individuals, EBV can promote tumor formation.

Cytomegalovirus (CMV): CMV is another herpes virus and it is shed in urine after reactivation. In addition to causing very serious congenital diseases in fetuses and newborns, it can lead to an infectious mononucleosis-type of disease in adults. This virus is found in the tissues of epithelial origin (i.e., kidney, liver, salivary glands, gut epithelium) and fibroblasts.

Varicella zoster (VZV): VZV is the etiological agent of chickenpox (primary) and shingles. VZV becomes latent in human ganglia after primary infection. VZV reactivation occurs most frequently in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated and humoral immunity to the virus. VZV can reactivate following the stress of surgery and also in response to various non-surgical stressors.

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Cohrs RJ, Mehta SK, Schmid DS, Gilden DH, Pierson DL. Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts. Journal of Medical Virology. 2008 June; 80(6):1116-22.[]

Crucian BE, Stowe RP, Pierson DL, Sams CF. Routine detection of Epstein-Barr virus specific T-cells in the peripheral blood by flow cytometry. J Immunol Methods. 2001 Jan 1;247(1-2):35-47. []

Mehta SK, Cohrs RJ, Forghani B, Zerbe G, Gilden DH, Pierson DL. Stress-induced subclinical reactivation of varicella zoster virus in astronauts. J Med Virol. 2004 Jan;72(1):174-9. []

Mehta SK, Stowe RP, Feiveson AH, Tyring SK, Pierson DL. Reactivation and shedding of cytomegalovirus in astronauts during spaceflight. J Infect Dis. 2000 Dec;182(6):1761-4. Epub 2000 Nov 8. []

Payne DA, Mehta SK, Tyring SK, Stowe RP, Pierson DL. Incidence of Epstein-Barr virus in astronaut saliva during spaceflight. Aviat Space Environ Med. 1999 Dec;70(12):1211-3. []

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. []

Stowe RP, Cubbage ML, Sams CF, Pierson DL, Barrett AD. Detection and quantification of Epstein-Barr virus EBER1 in EBV-infected cells by fluorescent in situ hybridization and flow cytometry. J Virol Methods. 1998 Nov;75(1):83-91. []

Stowe RP, Mehta SK, Ferrando AA, Feeback DL, Pierson DL. Immune responses and latent herpesvirus reactivation in spaceflight. Aviat Space Environ Med. 2001 Oct;72(10):884-91. []

Stowe RP, Pierson DL, Barrett AD. Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts. Psychosom Med. 2001 Nov-Dec;63(6):891-5. []

Stowe RP, Pierson DL, Feeback DL, Barrett AD. Stress-induced reactivation of Epstein-Barr virus in astronauts. Neuroimmunomodulation. 2000;8(2):51-8. []

Stowe RP, Sams CF, Pierson DL. Effects of mission duration on neuroimmune responses in astronauts. Aviat Space Environ Med. 2003 Dec;74(12):1281-4.[]

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Data Information
Data Availability
Archive is complete. Data sets are not publicly available but can be requested.
Data Sets+ Request data

Blood Marker: Cytokines (IL4 and IL10)
Blood Marker: Viral Antibody Titer
Blood Marker: Viral DNA
Saliva Markers: IgA
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Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
STS-100 04/19/2001 05/01/2001 12 days
STS-101 05/19/2000 05/29/2000 10 days
STS-102 03/08/2001 03/21/2001 13 days
STS-104 07/12/2001 07/24/2001 13 days
STS-106 09/08/2000 09/20/2000 12 days
STS-109 03/01/2002 03/12/2002 11 days
STS-110 04/08/2002 04/19/2002 11 days
STS-112 10/07/2002 10/18/2002 11 days
STS-113 11/23/2002 12/07/2002 14 days
STS-114 07/26/2005 08/09/2005 14 days
STS-115 09/09/2006 09/21/2006 12 days
STS-116 12/09/2006 12/22/2006 13 days
STS-118 08/08/2007 08/21/2007 13 days
STS-121 07/04/2006 07/17/2006 13 days
STS-72 01/11/1996 01/20/1996 9 days
STS-75 02/22/1996 03/09/1996 16 days
STS-77 05/19/1996 05/29/1996 10 days
STS-78 06/20/1996 07/07/1996 17 days
STS-82 02/11/1997 02/21/1997 10 days
STS-83 04/04/1997 04/08/1997 4 days
STS-85 08/07/1997 08/19/1997 12 days
STS-92 10/11/2000 10/24/2000 13 days
STS-93 07/23/1999 07/27/1999 5 days
STS-94 07/01/1997 07/17/1997 16 days
STS-97 11/30/2000 12/11/2000 11 days
STS-99 02/11/2000 02/22/2000 11 days

Additional Information
Managing NASA Center
Johnson Space Center (JSC)
Responsible NASA Representative
Johnson Space Center LSDA Office
Project Manager: Jessica Keune
Institutional Support
National Aeronautics and Space Administration (NASA)
Alternate Experiment Name
Virus Shed
Latent Virus
Proposal Source
Hardware Items