Space Flight Induced Reactivation of Latent Epstein-Barr Virus (Epstein-Barr) - 12.03.13
Science Objectives for Everyone
The Space Flight-Induced Reactivation of Latent Epstein-Barr Virus (Epstein-Barr) experiment performs tests to study changes in the human immune function using blood and urine samples collected before and after space flight. The study will provide insight for possible countermeasures to prevent the potential development of infectious illness in crewmembers during flight.
Science Results for Everyone
Up to 95 percent of people have been infected at some point with the Epstein-Barr virus (EBV), which has been linked to mononucleosis, lymphoma, and other diseases. EBV can lie dormant in the body for years, only to be reactivated by stressful events– including space flight. The Space Flight-Induced Reactivation of Latent Epstein-Barr Virus investigation clearly show reactivation of the EBV virus in ISS crew members, especially those who flew longer, and dramatic increase in EBV gene replication compared to healthy controls. Further understanding of a crew member’s immune response to unique mission physical and psychological demands, and stress levels is needed to balance crew health, mission requirements, and stress-inducing factors.
Johnson Space Center, Human Research Program, Houston, TX, United States
National Aeronautics and Space Administration (NASA)Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)Research Benefits
Information PendingISS Expedition Duration:
June 2002 - October 2008Expeditions Assigned
5,6,11,12,13,14,15,16,17Previous ISS Missions
Epstein-Barr was performed during ISS Expeditions 5, 6 and 11 - 17.
- As space flight mission durations increase, the potential development of infectious illness in crewmembers during flight also increases. This is especially true with latent viruses (viruses that lie dormant in cells, such as herpes viruses that cause cold sores) and infections caused by these viruses which are not mitigated by a quarantine period.
- An example of a latent infection is Epstein-Barr virus, of which approximately 90 percent of the adult population is infected. Stress and other acute/chronic events reactivate this virus from latency, which results in increased virus replication.
- Space Flight-Induced Reactivation of Latent Epstein-Barr Virus (Epstein-Barr) will assess the immune system response to this virus using blood and urine samples collected before and after space flight.
In the United States, approximately 95% of adults have been infected with Epstein-Barr Virus (EBV), one of the most common of human viruses and a member of the herpes virus family. EBV is an initial infection that establishes a lifelong dormant infection inside the body that can be reactivated by illness or stress. Once active, EBV causes infectious mononucleosis, cancers, and other disorders associated with the lymphatic system in people with a compromised immune system.
The decreased cellular immune function experienced by astronauts in space flight is likely caused by a combination of the microgravity environment and the stresses associated with a mission. With longer-duration missions, it is hypothesized that latent viruses are more likely to be reactivated, placing the crew at risk of developing and spreading infectious illnesses and jeopardizing the mission. Preliminary studies of astronauts have shown increased EBV shedding (the means by which viruses reproduce) in the saliva and increased antibody titers to the virus?s proteins.
Epstein-Barr examined levels to which the crews? immune systems were suppressed during space flight and identifying conditions under which the virus may reactivate. To conduct Epstein-Barr, investigators collected urine and blood samples preflight and again postflight. The samples were analyzed for the presence of stress hormones and cytokines (messengers of the immune system), EBV replication, and virus-specific T-cell immune function. Epstein-Barr used the levels to which the crews? immune systems are suppressed during space flight to determine conditions under which EBV may reactivate.
In the United States, approximately 90 percent of adults have been infected with Epstein-Barr virus (EBV), one of the most common human viruses. It establishes a lifelong dormant infection inside the body, but can be reactivated by illness or stress. Once active, it can cause infectious mononucleosis (also known as mono). Decreased cellular immune function is observed during and after human space flight. With longer duration space missions, latent viruses are more likely to become reactivated, placing the crew at risk of developing and spreading infectious illness. If this is the case, drug therapies must be created to protect crewmembers during long-term and interplanetary missions (i.e. trips to Mars). This study will help provide information related to immune function and virus activity in space to develop such remedies and ensure future exploratory space missions.Earth Applications
This type of study could shed more light on infectious diseases, how they are related to stress here on Earth and how they can be treated.
Epstein-Barr has no inflight requirements.Operational Protocols
The investigators will collect urine and blood samples preflight at launch minus (L-180, L-44, L-10, and L-3) and again after flight return plus (landing day, R+3, R+14, and R+180) from Station expedition crews (starting with Expedition 5) for a total of 18 subjects. For Shuttle crews (starting with STS-108) samples will be collected preflight (L-180, L-65, L-10 and L-3) and again after flight (landing day, R+3, R+14 and R+180) for a total of 62 participants.
Nearly everyone worldwide (up to 95%) has been infected at some point during life with the Epstein-Barr virus (EBV) - a member of the herpesvirus family. EBV has been linked to a variety of diseases such as infectious mononucleosis, malignant lymphomas, and nasopharyngeal carcinoma. After primary infection, the virus lies dormant lifelong in the host to avoid detection by the immune system but can be "reactivated" by a number of stressors including those associated with space flight such as preflight stress and immune system changes during flight. A goal of the EBV study was to determine whether changes in EBV gene expression (reactivation) occurred after short- and long-duration space flight. All astronaut and control subjects (24) tested positive for antibodies indicating past EB infection. Peripheral blood samples were collected from 12 astronauts 10 days before launch and on landing/recovery day. The mean mission length for Shuttle astronauts was 11 days, while the mean mission length for ISS astronauts was 180 days.
In Shuttle astronauts, a pattern of immediate-early and early viral gene transcription (the first step in gene production) was observed indicative of EBV reactivation. Altogether, there was a significant increase in the number of immediate early and early gene replications in Shuttle astronaut samples as compared to healthy control samples. Although EBV reactivation did occur in Shuttle astronauts, productive EBV replication in peripheral blood B-lymphocytes did not. In contrast, samples from three ISS astronauts after flight show strong evidence that complete productive EBV replication is occurring in the peripheral blood B-cells of these astronauts, and data clearly show activation of the full cascade of replicative EBV gene expression in the B-cells of ISS astronauts. For these crewmembers who flew longer (6 month) in space, latent gene expression and late lytic (involves the destruction of the host cell) gene transcripts were both more frequent and diverse. Overall, there was a significant increase in the number of immediate early and early gene transcripts in ISS astronaut samples as compared to healthy control samples and Shuttle astronauts at landing. The authors acknowledged there were limitations to this study. First, the sample size was limited (the results, however, were quite striking). Second, data from other potential stressors (e.g., sleep deprivation, changes in circadian rhythms, etc.), known to affect immune function, were not available. Additionally, increased radiation exposure on long-duration missions may also affect cellular immunity. Another consideration is that only postflight samples were analyzed and do not necessarily reflect EBV gene expression during flight (Stowe 2011).
A related study focused on a type of white blood cells called monocytes which play multiple roles within the immune system. Evidently, the more complex and greater the workloads and associated stress crewmembers experienced, the more their immune function, in this case monocyte parameters, appeared to be compromised, mainly in the reduction of the body’s defense signaling capability and pronounced suppression of the immune system’s ability to identify and neutralize potential pathogens. Researchers also found increases in the stress hormone cortisol in Shuttle crewmembers, presumably due to the rigors of preflight training, which were accompanied by significant changes in white blood cells even days prior to launch. It is important to note, however, that for short-duration crewmembers, these immune system changes do not appear to linger beyond a few days after mission completion. Further understanding that unique mission variables and stress levels can elicit specific immune responses in space flight crewmembers is crucial for mission planners as they strive to maintain a balance between optimum crew health, mission requirements, and stress inducing factors especially on prolonged missions. While the clinical significance of these findings remain to be determined, they are potentially significant for the health of astronauts who will spend long periods in space and could pose a health risk for crewmembers following prolonged space travel, in particular due to the lack of specialized medical facilities in case of injury or illness. (Stowe 2011, Crucian 2011).
Stowe RP, Kozlova EV, Sams CF, Pierson DL, Walling DM.Latent and lytic Epstein-Barr virus gene expression in the peripheral blood of astronauts. Journal of Medical Virology. 2011; 83(6): 1071-1077.
Mehta SK, Crucian BE, Stowe RP, Simpson RJ, Ott CM, Sams CF, Pierson DL. Reactivation of latent viruses is associated with increased plasma cytokines in astronauts. Cytokine. 2012; 61(1): 205-209. DOI: 10.1016/j.cyto.2012.09.019. PMID: 23107825.
Stowe RP, Sams CF, Pierson DL.Adrenocortical and Immune Responses Following Short- and Long-Duration Spaceflight. Aviation, Space, and Environmental Medicine. 2011 Jun; 82(6): 627-634. DOI: 10.3357/ASEM.2980.2011. PMID: 21702314.
Crucian BE, Stowe RP, Pierson DL, Sams CF. Immune System Dysregulation Following Short- Vs Long-Duration Spaceflight. Aviation, Space, and Environmental Medicine. 2008 September; 79(9): 835-843. DOI: 10.3357/ASEM.2276.2008. PMID: 18785351.
Ground Based Results Publications
Stowe RP, Barrett AD, Pierson DL. Space flight-induced reactivation of latent Epstein-Barr virus. Conference and Exhibit on International Space Station Utilization, Cape Canaveral, FL; 2001
Pierson DL, Stowe RP, Phillips TM, Lugg DJ, Mehta SK. Epstein-Barr Virus Shedding by Astronauts During Space Flight. Brain, Behavior, and Immunity. 2005; 19(3): 235-242. DOI: 10.1016/j.bbi.2004.08.001. PMID: 15797312.
Stowe RP, Pierson DL, Barrett AD. Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts. Psychosomatic Medicine. 2001; 63(6): 891-895.
Sonnenfeld G. The immune system in space and microgravity. Medicine and Science in Sports and Exercise. 2002; 34(12): 2021-2027.
Stowe RP, Pierson DL, Feeback DL, Barrett AD. Stress-induced reactivation of Epstein-Barr virus in astronauts. NeuroImmunoModulation. 2000; 8(2): 51-58.
A colored, computer generated depiction of an Epstein-Barr virus particle.
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Epstein-Barr virus shown using the fluorescent antibody staining technique.
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