Incidence of Latent Virus Shedding During Space Flight (Latent Virus) - 07.14.16
The Incidence of Latent Virus Shielding During Spaceflight (Latent Virus) study will support and expand information on latent viruses - or those inactive in the human system - that can reactivate in space flight, such as a cold sore. Latent virus reactivation may be an important threat to crew health during extended space missions, as crewmembers live and work in a closed environment. Potential applications of this research include the development of a rapid and sensitive diagnostic method for identifying crewmembers at increased risk of illness due to viral infections. New technology from this investigation benefits both NASA and commercial applications. Science Results for Everyone
Warning: latent viruses on board! Latent or inactive viruses in our bodies can reactivate in space flight, posing a potential threat to crew health. This investigation, which studied Epstein-Barr (EBV) and Varicella zoster (VZV) viruses, suggest that reactivation may be caused by increased stress. Reactivation of EBV appeared to increase at all phases of space flight, while VZV increased as space flight approached and decreased post-flight. The type, level, and combination of stresses experienced, as well as the different ways individuals cope with stress, may influence this reactivation. The results could help develop a way to identify crew members at increased risk of viral infections. Experiment Details
Duane L. Pierson, Ph.D., Johnson Space Center, Houston, TX, United States
Satish K. Mehta, Ph.D., Enterprise Advisory Services Incorporated, Houston, TX, United States
NASA Johnson Space Center, Human Research Program, Houston, TX, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
Human Exploration and Operations Mission Directorate (HEOMD)
ISS Expedition Duration
November 2000 - August 2001; December 2001 - December 2002; April 2005 - October 2005; April 2006 - October 2007
Latent Virus has been performed on many Shuttle missions, including STS-107 (Columbia), which was lost in 2003.
- Risks associated with most bacterial, fungal, viral and parasitic pathogens can be reduced by a suitable quarantine period before the flight and by appropriate medical care. However, latent viruses (viruses that lie dormant in cells, such as herpes viruses that cause cold sores) already inside the cells of crewmembers are unaffected by such actions and pose an important infectious disease risk to crewmembers involved in space flight and space habitation.
- Weakening of the immune system of astronauts that may occur in the space environment could allow increased reactivation of the latent viruses and increase the incidence and duration of viral shedding. Such a result may increase the concentration of herpes and other viruses in the spacecraft.
Latent herpes viruses pose an important infectious disease risk to crewmembers involved in space flight and space habitation. The risk certainly increases as the mission duration increases. Risks that are associated with most bacterial, fungal, viral, and parasitic pathogens can be reduced by a suitable quarantine period before the flight and by appropriate medical care. However, latent viruses are unaffected by such actions. The observed decrements in the immune response resulting from space flight may allow increased reactivation of the same herpes viruses and may increase the incidence and duration of viral shedding. Such a result may increase the concentration of herpes viruses in the spacecraft. Particulates (including viruses) do not settle out of the air in the microgravity conditions of space flight. Additional characteristics of space flight, such as living in relatively crowded conditions in a closed environment and using recycled air and water, will increase the potential for transfer of viruses among the crewmembers. This study will help determine the characteristics of viral parameters such as latent virus reactivation, shedding, and crew exchange during space flight, and is an integral part of ongoing efforts to accumulate microbiological data concerning the exposure of astronauts to potentially infectious agents.
Latent virus reactivation may be an important threat to crew health during the longer duration exploration missions as crewmembers live and work in a closed environment. This investigation will aid in determining the clinical risk of asymptomatic reactivation and shedding of latent viruses to astronaut health, and the need for countermeasures to mitigate the risk. Stress-induced viral reactivation may also prove useful in monitoring early changes in immunity prior to onset of clinical disease.
The viral-specific saliva DNA test currently used for space flight investigations may be applied to the rapid diagnosis of herpes virus disease in clinics. These studies of latent virus reactivation in the very healthy, superbly conditioned flight crews may provide new insight into stress, immunity, and viral disease in the general population.
Operational Requirements and Protocols
Saliva samples are collected daily during the mission (beginning on Flight Day 2). Immediately after awakening and prior to brushing teeth, the crewmember retrieve a Collection Bag Assembly containing an unused cotton plug from the personalized Saliva Kit. The cotton plug is placed in the mouth for two minutes until the cotton plug is saturated with saliva. The saliva containing plug is placed back in the Collection Bag Assembly, the clip removed, the swab mixed with the liquid preservative, and the clip replaced. The Collection Bag Assembly is labeled with the MET and stowed in the personalized Saliva Kit Assembly in the compartment labeled,"Used". During the sample collection period, medications and stressful conditions are recorded. In the event of a cold sore, a sample of the lesion is collected with a viral Culturette.
Crewmembers collect saliva samples every other day from about 180 to 150 days before the launch (L-180 to L-150) of space shuttle, every day during flight, and every day after flight for two weeks ( R+1 to R+14). During the sample collection period, medications and stressful conditions are recorded. In addition, blood and urine samples are collected at 10 days before the launch, at landing and at the annual medical exam of the astronauts. Saliva and urine samples are analyzed using the polymerase chain reaction (PCR) to detect the presence of three important herpes viruses (Epstein-Barr virus and Varicella zoster virus (from saliva), and cytomegalovirus (from urine). The PCR technique allows the detection of both symptomatic and asymptomatic shedding. Viral antibody titers for these herpes viruses are measured by indirect immunofluoresence in plasma. Stress hormones like cortisol and catecholamines are measured in plasma and urine samples collected at different time points.
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Many of the biological samples that are collected from astronauts immediately before and following space flight have proven valuable for several investigators. Saliva samples collected from crew members traveling on the Shuttle to and from ISS, since 2000, have provided preliminary results for the Latent Virus investigation. For this investigation, Epstein-Barr (EBV) and Varicella zoster (VZV) viruses were studied using the saliva samples. The data that were collected indicate that latent viruses can become infectious under stressful conditions such as space flight.
Thirty-two healthy astronauts were studied for EBV reactivation on ten space shuttle missions since 2000. This study revealed that the increased stress of space flight may cause latent virus reactivation in astronauts. The astronauts who were studied served as either commander, pilot or mission specialists; these are all different positions that carry their own unique stresses. Potential EBV reactivation in astronauts was shown by three measures, EBV presence in saliva, number of copies of viral EBV DNA in saliva and titer of antibodies to EBV viral antigens. Data revealed that there was no correlation between the shedding frequency of EBV in the saliva and the amount of EBV DNA in the saliva. EBV antibody titers increased before flight and continued to increase three days post flight. The amount of EBV DNA increased as the number of days in space increased. The pattern and amount of EBV shedding in the astronauts likely correlated to various events that occurred during space flight. The types, levels and combination of stresses experienced before, during and after flight, as well as the different ways individuals cope with stress may result in changes in the EBV shedding frequency (Pierson 2005).
Eight healthy astronauts were studied during three shuttle missions to determine the cause of VZV reactivation in a healthy adult astronaut two days before flight. Ten subjects (not astronauts) that remained on Earth were used as controls in this investigation. Polymerase Chain Reaction (PCR) analysis was performed on DNA samples extracted from the saliva of the subjects. Before flight all samples from the experimental subjects were negative for VZV DNA, during flight VZV DNA was detected in 87% of the astronauts, following return to Earth VZV DNA was detected in only 19% of the astronauts tested. During this same time frame no VZV DNA was detected in saliva samples of the control subjects. VZV, like EBV, can reactivate during stressful situations such as space flight (Mehta 2004).
Each virus--EBV and VZV--has its own unique timing when reactivation due to stress. EBV appeared to increase at all phases of space flight (preflight, in-flight and postflight), while VZV DNA increased as space flight approached and decreased postflight. (Evans et al. 2009)
Mehta SK, Cohrs RJ, Forghani B, Zerbe G, Gilden DH. Stress-induced Subclinical Reactivation of Varicella Zoster Virus in Astronauts. Journal of Medical Virology. 2004; 72: 174-179. DOI: 10.1002/jmv.10555.
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.
Ground Based Results Publications
Crucian BE, Stowe RP, Mehta SK, Yetman DL, Leal MJ, Quiriarte HD, Pierson DL, Sams CF. Immune Status, Latent Viral Reactivation, and Stress During Long-Duration Head-Down Bed Rest. Aviation, Space, and Environmental Medicine. 2009; 80(5): 37-44. DOI: 10.3357/ASEM.BR05.2009.
Mehta SK, Stowe RP, Feiveson AH, Tyring SK, Pierson DL. Reactivation and shedding of cytomegalovirus in astronauts during space flight. Journal of Infectious Diseases. 2000; 182(6): 1761-1764. DOI: 10.1086/317624.
Stowe RP, Sams CF, Pierson DL. Effects of Mission Duration on Neuroimmune Responses in Astronauts. Aviation, Space, and Environmental Medicine. 2003 December; 74(12): 1281-1284.
Payne DA, Mehta SK, Tyring SK, Stowe RP, Pierson DL. Incidence of Epstein-Barr Virus in Astronaut Saliva During Space Flight. Aviation, Space, and Environmental Medicine. 1999 December; 70(12): 1211-1213. PMID: 10596777.
Mehta SK, Pierson DL, Cooley H, Dubow R, Lugg DJ. Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners. Journal of Medical Virology. 2000 June; 61(2): 235-240. DOI: 10.1002/(SICI)1096-9071(200006)61:2<235::AID-JMV10>3.0.CO;2-4.
Microscopy image of a herpes virus, one of several latent viruses that will be studied during the Latent Virus investigation. Image courtesy of Linda Stannard, of the Department of Medical Microbiology, University of Cape Town, South Africa.
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Computer generated image of cytomegalovirus (CMV).
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Electron micrograph of the chicken pox virus, the bar represents 100 nm. Naked capsids are seen. Image courtesy of Dr. Frank Fenner, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
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