The Essentials
- In space, astronauts' immune systems are disrupted, primarily due to microgravity.
- One of the consequences is the reactivation of certain viruses, such as herpesviruses, which remain in a latent state in the body.
- This problem, which compounds the other health effects on astronauts caused by long stays in space, calls into question the feasibility of missions to distant celestial bodies.
This warning highlights the physiological and medical challenges faced by organizers of long-distance space missions. Beyond the effects of microgravity on muscles, bones, the cardiovascular system, and the eyes, another question deserves our attention: How does our immune system respond to a prolonged stay in space?
Research conducted over the past several years aboard the International Space Station (ISS) reveals that several immune functions can be altered during spaceflight—and sometimes after returning to Earth. In particular, the distribution of immune cells, the production of cytokines (chemical messengers that play a key role in coordinating the immune system and inflammation), and the functions of T cells and NK (natural killer) cells—which are involved in antiviral surveillance— can be affected.
What happens when the mechanisms responsible for controlling persistent infections become less effective? Research on latent viruses—which can remain in the body for years—provides some answers.
Silent viruses, but never eliminated
After an initial infection, some viruses persist in the body without causing symptoms. Among these latent viruses are the human herpesviruses (HHV), a family of viruses that includes, among others, the Epstein-Barr virus (EBV, which causes infectious mononucleosis), cytomegalovirus (CMV), varicella-zoster virus (VZV, which causes chickenpox and shingles), and herpes simplex virus type 1 (HSV-1, which causes herpes, or “cold sores”).
Among these viruses capable of entering a latent state, EBV infects the vast majority of the world’s population and persists primarily in B cells. VZV, on the other hand, remains in sensory neurons and can reactivate years later in the form of shingles.
Generally speaking, during the latent phase, viral gene expression is severely limited. The immune system keeps the virus under control, but is unable to eliminate it entirely: if this balance is disrupted, the virus can reactivate.
Factors Contributing to the Reactivation of Human Herpesviruses Human herpesviruses can reactivate years after infection. This reactivation varies depending on the site of latency (the tissue site where the viral genome is present) and immune control mechanisms.
Psychological stress, fatigue, lack of sleep, fever, and radiation (UV or gamma, etc.) can promote certain reactivations, particularly those of herpesvirus type 1 (HSV-1). Immunosuppression and immunosuppressive treatments play a major role in the reactivation of EBV, CMV, HHV-6, and other HHVs. These factors act through neuroendocrine mechanisms —cells of the neuroendocrine system are similar to nerve cells (neurons), except that they produce and release hormones in response to signals they receive from the nervous system— as well as through immune and cellular mechanisms ; however, their role and the level of evidence supporting them differ depending on the virus.
Does such viral reactivation necessarily mean that a person will become ill? Not necessarily. While reactivation may be accompanied by clinical symptoms under certain circumstances, it can often remain asymptomatic. In such cases, it is detected only through the presence of viral DNA in saliva and blood.
An important point to note: the detection of the viral genome does not, by itself, prove the production of new infectious viruses. This distinction is essential for interpreting the results obtained from astronauts.
What do we observe in astronauts?
As early as the 2000s, studies conducted by NASA teams documented cases of reactivation or shedding of several human Herpesviridae in astronauts.
Studies involving International Space Station (ISS) crew members have revealed an increase in the frequency and duration of detection of DNA from certain viruses—including EBV, VZV, and CMV—during space missions. Other studies have also reported the detection of EBV, VZV, and HSV-1 in saliva, as well as CMV in urine.
Is microgravity the sole cause of these reactivations? The data currently available do not support this conclusion. Astronauts are, in fact, simultaneously exposed to several stressors: flight duration, physiological stress, confinement, sleep disturbances, and radiation. The effects of these stressors may combine and contribute to the observed immune changes.
Viral reactivation is thus a useful indicator of the interactions between the organism and its spatial environment, but the precise mechanisms and the respective contributions of these factors remain to be elucidated.
What mechanisms could explain these observations?
Astroimmunology studies the effects of spaceflight and the associated stresses on the immune system. It is known that microgravity can alter the organization and signaling of immune cells, while ionizing radiation—particularly galactic cosmic rays— represents another source of biological stress.
In addition to these factors , there is psychological stress, isolation, and disruptions to circadian rhythms. Changes in neuroendocrine responses—particularly those involving cortisol and catecholamines—can also interact with immune functions.
How do these factors interact? An impairment in the T-cell response can, for example, compromise the control of infected cells, while other physiological changes can influence the balance between viral latency and reactivation.
However, it remains difficult to quantify the respective contributions of these mechanisms in humans.
EBV is a particularly interesting model among human Herpesviridae because it persists in the body for life while retaining a remarkable ability to constantly reactivate its lytic cycle (the mode of viral production that leads to the lysis—that is, the destruction—of the host cell).
Could a monitoring approach that combines viral DNA quantification, detection of markers of lytic activity, and analysis of EBV-specific T cells help to better characterize this reactivation in astronauts? This approach has yet to be evaluated. Indeed, a biological marker alone does not constitute evidence of clinical risk.
From the ISS to Mars: How Can We Anticipate Viral Risks on Long-Distance Missions?
The observations gathered on the ISS raise a crucial question for missions to the Moon and Mars: How can we anticipate the potential consequences of viral reactivation when access to medical care and return to Earth will be difficult?
The cumulative effects of microgravity, radiation, confinement, and sleep disturbances on astronauts' physiology and mental health remain poorly understood.
Longitudinal studies—that is, studies conducted over extended periods—will need to determine whether certain virologic and immunological markers can distinguish between transient reactivation with no clinical consequences and a situation that poses a health risk.
For EBV, this research could involve quantifying viral DNA, analyzing markers of the lytic cycle, and characterizing specific immune responses. Studying additional markers for CMV and VZV would allow for the expansion of this surveillance.
The goal would not be to systematically treat every instance of viral detection: an asymptomatic reactivation does not automatically warrant antiviral treatment. Rather, the aim would be to identify potential markers associated with an unfavorable outcome and to assess their predictive value.
Beyond space exploration, this research could shed light on the mechanisms of viral persistence in immunocompromised individuals on Earth. Understanding how the body controls viruses in space also means gaining a better understanding of the delicate balance between our immune defenses and infectious agents capable of persisting for a lifetime.
