Reactivation and Shedding of Cytomegalovirus in Astronauts during Spaceflight

Mehta, Satish K.; Stowe, Raymond P.; Feiveson, Alan H.; Tyring, Stephen K.; Pierson, Duane L.

doi:10.1086/317624

Cited by 190 publications

(123 citation statements)

References 15 publications

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“…The finding of a low antigenemia rate in myelodysplastic syndrome, a preleukemic, less severe disease, is consistent with this feature (Table 1). Mucosal or epithelial (local) reactivation may occur during subclinical levels of stress, such as during space flight in astronauts (15). CMV antigenemia, on the other hand, represents a systemic form of reactivation that probably occurs only under conditions of severe immunocompromise, as was known previously (18) and seen in this study.…”

Section: Discussionsupporting

confidence: 74%

Epidemiologic Analysis of Reactivated Cytomegalovirus Antigenemia in Patients with Cancer

Han

2007

J Clin Microbiol

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The epidemiologic features of reactivated cytomegalovirus (CMV) antigenemia were studied among 4,382 cancer patients who were cared for and tested at the University of Texas M. D. Anderson Cancer Center from 2001 to 2004. The effects of stem cell transplant (SCT) status, underlying disease, age, sex, ethnicity, and antibody status (prior to CMV exposure) on the incidence of CMV antigenemia were determined; and the CMV burdens were quantified. Antigenemia occurred in 9.3% of patients with non-SCT (n ‫؍‬ 2511), 12.0% with autologous SCT (n ‫؍‬ 582), and 39.1% with allogeneic SCT (n ‫؍‬ 1289). Non-SCT patients with lymphoid tumors had a significantly higher rate of antigenemia than those with myeloid tumors (13.6% versus 3.9%) (P < 0.001); however, after allogeneic SCT, the underlying diseases had little effect, except for multiple myeloma (56.8%) (P ‫؍‬ 0.014). Among the allogeneic SCT recipients, higher CMV antigenemia rates were also associated with female sex, older age, and positivity for pre-SCT CMV antibody. Depending on the underlying disease and its associated initial CMV risk, allogeneic SCT increased the risk by 2.6-to 29.6-fold (overall, 4.0-fold). With or without SCT, Asians had the highest CMV antigenemia rates and burdens, followed by blacks, Hispanics, and whites, and these partially correlated with antibody prevalence. Among the 808 patients with antigenemia, the circulating peak CMV burden was significantly higher among non-SCT patients (geometric mean, 18.7 positive cells per 10 6 leukocytes) than among allogeneic SCT patients (geometric mean, 7.7 positive cells per 10 6 leukocytes) or autologous SCT patients (geometric mean, 7.0 positive cells per 10 6 leukocytes) who underwent monitoring for CMV. Together, these results allow stratification of CMV risks and suggest a substantial CMV reactivation among non-SCT cancer patients and, thus, the need for better diagnosis and control.Human cytomegalovirus (CMV), a ␤-herpesvirus, causes a variety of infections, such as congenital infections in neonates, infectious mononucleosis in healthy individuals, and reactivation in immunocompromised patients (18). CMV reactivation is a common and severe problem in organ and stem cell transplant (SCT) recipients and in those infected with human immunodeficiency virus (HIV), particularly before the era of effective antiretroviral therapy. Among SCT recipients, the rate of CMV reactivation in the bloodstream (antigenemia or viremia) has been reported to be from 30% to 70% (2, 11, 13). Routine monitoring of CMV antigenemia by testing for the CMV pp65 antigen (or other means) has played a crucial role in detecting the virus and guiding effective antiviral therapy in SCT recipients (4, 16).The incidence of CMV antigenemia among patients who have severe underlying diseases, such as leukemia, lymphoma, or solid tumors, but who are not transplant recipients or HIV infected is largely unknown. In this population, CMV antigenemia has been reported only in small series or case studies (7-9). Even among SCT and organ transpla...

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Section: Discussionsupporting

confidence: 74%

Epidemiologic Analysis of Reactivated Cytomegalovirus Antigenemia in Patients with Cancer

Han

2007

J Clin Microbiol

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“…Although none of the studies on latent infections in the elderly have addressed the potential role of stress, several reports on younger persons have, in fact, shown an association between reduced control over latent viruses and concomitant increases in stress and/or elevated levels of serum cortisol. For example, in astronauts, reactivation of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are correlated with increased stress hormone levels associated with space flight (Stowe et al, 2001;Mehta et al, 2000). Stress is associated with re-emergence of varicella zoster (shingles) and herpes labialis (Haynes & Swain, 2006).…”

Section: Discussionmentioning

confidence: 99%

Reduced telomerase activity in human T lymphocytes exposed to cortisol

Choi¹,

Fauce²,

Effros³

2008

Brain, Behavior, and Immunity

311

208

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Accelerated telomere shortening in lymphocytes has been associated with a variety of human pathologies, including HIV disease, Down syndrome, and cardiovascular disease. Recent findings indicate that reduced telomere length is also associated with chronic psychological stress and mood disorders. Telomerase, which prevents telomere shortening, can be upregulated in T lymphocytes in concert with activation, thereby retarding telomere shortening. Here, we demonstrate that exposure of human T lymphocytes to cortisol is associated with a significant reduction in telomerase activity both during primary stimulation of resting cells and secondary stimulation of previously activated cells. The effect is observed in both CD4 and CD8 T lymphocytes, and is associated with reduced transcription of hTERT, the telomerase catalytic component. These findings provide a potential mechanism for stress-associated telomere length attrition, and suggest that strategies to enhance T lymphocyte telomerase activity may provide beneficial effects on immune function in situations of chronic emotional stress.

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“…Two other human herpesviruses, cytomegalovirus and Epstein-Barr virus, have also been shown to reactivate during and after space flight (Mehta et aL, 2000;Payne et aL , 1999). Although the mechanism by which herpesviruses reactivate during space fl ight is unknown , the combination of gravitational changes and a confined , unfamiliar environment (extreme isolation from family in a crowded environment, lack of privacy, sleep depravation , micro-gravity, physical and physiological stress) has been associated with increased levels of ACTH and cortisol during and after space flight 2001 b).…”

Section: Discussionmentioning

confidence: 99%

Stress‐induced subclinical reactivation of varicella zoster virus in astronauts

Mehta

Cohrs

Forghani

et al. 2003

Journal of Medical Virology

234

158

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Abstract.After primary infection , varicella-zoster virus (VZV) becomes latent in ganglia. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients , and patients with cancer and AIDS , correlating with a specific decl ine in cellmediated immunity to VZV. VZV can also reactivate after surgical stress. To determine whether VZV can also reactivate after acute non-su rgical stress , we examined total DNA extracted from 312 saliva samples of eight astronauts before, during and after space flight for VZV DNA by PCR: 112 samples were obtained 234 to 265 days before fl ight, 84 samples on days 2 through 13 of space flight , and 116 samples on days 1 through 15 after flight. Before space flight only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight , 61 of 200 (30%) saliva samples were positive in all 8 astronauts . No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These data indicate that VZV can reactivate subclinically in healthy individuals after acute stress.Introduction. Primary VZV infection typically causes childhood varicella (chickenpox), after which virus becomes latent in cranial nerve , dorsal root and autonomic ganglia along the entire human neuraxis. Virus reactivates primarily in elderly individuals , as well as in organ transplant recipients and in patients with cancer and AIDS. Reactivation correlates with a specific decline in cell-mediated immunity to VZV. Although VZV also reactivates after the stress of surgery, including orofacial surgery, the relationship of VZV reactivation to non-surgical stress has not been studied .

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Reactivation and Shedding of Cytomegalovirus in Astronauts during Spaceflight

Cited by 190 publications

References 15 publications

Epidemiologic Analysis of Reactivated Cytomegalovirus Antigenemia in Patients with Cancer

Epidemiologic Analysis of Reactivated Cytomegalovirus Antigenemia in Patients with Cancer

Reduced telomerase activity in human T lymphocytes exposed to cortisol

Stress‐induced subclinical reactivation of varicella zoster virus in astronauts

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