Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan.

Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.

Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults.

OBJECTIVE: Within the field of psychoneuroimmunology, much attention has been given to immune dysregulation and its impact on cognitive functioning. Some of this work has focused on the association between high levels of basal proinflammatory cytokines and poorer performance on measures of executive functioning; however, effect sizes have been quite small in human studies. METHODS: We investigated whether Epstein-Barr virus (EBV) antibody titers, a marker of immune dysregulation related to cellular immunity, may be associated with executive functioning while also attempting to replicate prior studies using two markers of proinflammatory cytokine production (i.e., circulating and lipopolysaccharide [LPS]-stimulated cytokines [interleukin 6, interleukin 1ß, interferon-γ]). A total of 71 community-dwelling adults (mean [standard deviation] age = 60.87 [6.26] years) who were seropositive for EBV infection participated in the study. RESULTS: Findings indicated that greater EBV antibody titers were associated with poorer performance on measures of the executive functions of inhibition ( B = -2.36, standard error = 1.06, p = .028) and cognitive flexibility ( B = -2.89, standard error = 1.13, p = .013) when including circulating and LPS-stimulated cytokines and other relevant covariates (i.e., age, sex, and body mass index) in linear regression analyses. Neither circulating nor LPS-stimulated cytokines were associated with performance on the cognitive tasks in the regression analyses. CONCLUSIONS: These results suggest that EBV antibody titers may be an indicator of immune dysregulation that is more relevant to executive functioning performance than either circulating or stimulated proinflammatory cytokines among community-dwelling adults.

Psychosocial stressors predict lower cardiovascular disease risk among Mexican-American adults living in a high-risk community: Findings from the Texas City Stress and Health Study.

The objective of this study was to examine the link between systemic and general psychosocial stress and cardiovascular disease (CVD) risk in a group of U.S. Latinos as a function of acculturation and education within the blended guiding conceptual framework of the biopsychosocial model of the stress process plus the reserve capacity model. We analyzed data from self-identifying Mexican-origin adults (n = 396, 56.9% female, Mage = 58.2 years, 55.5% < 12 years of education, 79% U.S.-born) from the Texas City Stress and Health Study. We used established measures of perceived stress (general stress), neighborhood stress and discrimination (systemic stress) to capture psychosocial stress, our primary predictor. We used the atherosclerotic CVD calculator to assess 10-year CVD risk, our primary outcome. This calculator uses demographics, cholesterol, blood pressure, and history of hypertension, smoking, and diabetes to compute CVD risk in the next 10 years. We also created an acculturation index using English-language use, childhood interaction, and preservation of cultural values. Participants reported years of education. Contrary to expectations, findings showed that higher levels of all three forms of psychosocial stress, perceived stress, neighborhood stress, and perceived discrimination, predicted lower 10-year CVD risk. Acculturation and education did not moderate the effects of psychosocial stress on 10-year CVD risk. Contextualized within the biopsychosocial and reserve capacity framework, we interpret our findings such that participants who accurately reported their stressors may have turned to their social networks to handle the stress, thereby reducing their risk for CVD. We highlight the importance of examining strengths within the sociocultural environment when considering cardiovascular inequities among Latinos.

Perceived Social Support and Latent Herpesvirus Reactivation: Testing Main and Stress-Buffering Effects in an Ethnically Diverse Sample of Adults.

OBJECTIVE: Perceived social support is consistently associated with physical health outcomes, and one potential physiological mechanism underlying this association is immune function. In this study, we tested both the main and stress-buffering effects of perceived social support on cellular immunity measured via latent herpesvirus reactivation. METHODS: Data were collected from a community-based sample of 1443 ethnically diverse adults between the ages of 25 and 90 years. Participants self-reported measures of perceived social support, stressful life events, daily hassles, and perceived stress, and provided a blood sample to assess antibody titers to the herpes simplex virus type 1 and Epstein-Barr virus (EBV). RESULTS: In accordance with the main effect hypothesis, results indicated that perceived social support was directly associated with EBV viral capsid antigen antibody titers (ß = -0.06, 95% confidence interval = -0.12 to -0.01, p = .029). Perceived social support, however, did not interact with stressful life events, daily hassles, or perceived stress to influence latent herpesvirus reactivation (p values > .05). Neither race/ethnicity nor age moderated any of the interactions between perceived social support and the stress measures on latent herpesvirus reactivation (p values > .10). CONCLUSIONS: Overall, the current study supports the main effect hypothesis, according to which higher levels of perceived social support were associated with lower levels of herpesvirus antibody titers.

Countermeasures-based Improvements in Stress, Immune System Dysregulation and Latent Herpesvirus Reactivation onboard the International Space Station - Relevance for Deep Space Missions and Terrestrial Medicine.

The International Space Station (ISS) has continued to evolve from an operational perspective and multiple studies have monitored both stress and the immune system of ISS astronauts. Alterations were ascribed to a potentially synergistic array of factors, including microgravity, radiation, psychological stress, and circadian misalignment. Comparing similar data across 12 years of ISS construction and operations, we report that immunity, stress, and the reactivation of latent herpesviruses have all improved in ISS astronauts. Major physiological improvements seem to have initiated approximately 2012, a period coinciding with improvements onboard ISS including cargo delivery and resupply frequency, personal communication, exercise equipment and protocols, food quality and variety, nutritional supplementation, and schedule management. We conclude that spaceflight associated immune dysregulation has been positively influenced by operational improvements and biomedical countermeasures onboard ISS. Although an operational challenge, agencies should therefore incorporate, within vehicle design limitations, these dietary, operational, and stress-relieving countermeasures into deep space mission planning. Specific countermeasures that have benefited astronauts could serve as a therapy augment for terrestrial acquired immunodeficiency patients.

Church Attendance and CMV Herpes Virus Latency Among Bereaved and Non-Bereaved Adults.

OBJECTIVE: There is widespread literature linking church attendance to physical health. However, little is known about the association of church attendance and the immune system, particularly during difficult life transitions. This study investigated the association between church attendance and CMV herpes-virus latency by assessing Cytomegalovirus (CMV) IgG antibody titers among bereaved and non-bereaved individuals. METHODS: Participants included 44 bereaved individuals and 44 controls with a mean age of 68 (SD=12.84). CMV herpes-virus latency was measured using CMV IgG antibody titers. Church attendance was measured using three items from the Community Healthy Activities Model Program for Seniors (CHAMPS) Questionnaire. RESULTS: After adjusting for participant's age, gender, education, minority status, weekly alcohol consumption, smoking, depression, body mass index (BMI) and comorbidities, church attendance was associated with lower CMV IgG antibody titers among bereaved and control participants. Further, there was a significant moderating effect of church attendance in the association between bereavement status and CMV IgG antibody titers, so that bereaved individuals attending church were found to have less herpes-virus reactivation (lower CMV IgG antibody titers) when compared to their bereaved counterparts that do not attend church. CONCLUSION: This study demonstrated that church attendance is associated with less herpes-virus reactivation as indexed by lower levels of CMV IgG antibody titers, particularly among the bereaved. Future studies should focus on further understanding the pathways by which church attendance impacts CMV herpes-virus latency during stressful life events, such as bereavement.

Sex differences in executive functioning and latent herpesvirus reactivation among bereaved and nonbereaved individuals.

The death of a spouse is a highly stressful event. Better executive functioning has been shown to benefit men to a greater degree than women during stress. We evaluated potential sex differences in stress and immune dysregulation among control and bereaved participants who completed a self-report measure of perceived stress, neuropsychological measures of inhibition and updating/monitoring of information in working memory, and a blood draw to measure Epstein-Barr virus (EBV) antibody titres. Moderation analyses were conducted to test the hypothesis that better inhibition would be associated with less stress and immune dysregulation among male bereaved participants compared with female bereaved participants. Bereaved females demonstrated greater EBV antibody titres than bereaved males. Male bereaved participants benefited from better inhibition, as evidenced by fewer EBV antibody titres, whereas bereaved female participants did not. In the control group, males with high inhibition reported lower stress than males with low inhibition. Present study results are an important step towards identifying those at greatest risk of stress and poor health.

Psychological and Biological Pathways Linking Perceived Neighborhood Characteristics and Body Mass Index.

BACKGROUND: Perceived neighborhood characteristics are linked to obesity, however, the mechanisms linking these two factors remain unknown. PURPOSE: This study aimed to examine associations between perceived neighborhood characteristics and body mass index (BMI), establish whether indirect pathways through psychological distress and inflammation are important, and determine whether these associations vary by race/ethnicity. METHODS: Participants were 1,112 adults enrolled in the Texas City Stress and Health Study. Perceived neighborhood characteristics were measured using the Perceived Neighborhood Scale. Psychological distress was measured with the Center for Epidemiological Studies Depression Scale, Perceived Stress Scale and mental health subscale of the Short Form Health Survey-36. Markers of inflammation included C-reactive protein, interleukin-6, and tumor necrosis factor receptor-1. Associations were examined with Structural Equation Modeling. RESULTS: A model linking neighborhood characteristics with BMI through direct and indirect (i.e., psychological distress and inflammation) paths demonstrated good fit with the data. Less favorable perceived neighborhood characteristics were associated with greater psychological distress (B = -0.87, ß = -0.31, p < .001) and inflammation (B = -0.02, ß = -0.10, p = .035). Psychological distress and inflammation were also significantly associated with BMI (Bdistress = 0.06, ß = 0.08, p = .006; Binflammation = 4.65, ß = 0.41, p < .001). Indirect paths from neighborhood characteristics to BMI via psychological distress (B = -0.05, ß = -0.03, p = .004) and inflammation (B = -0.08, ß = -0.04, p = .045) were significant. In multiple group analysis, a model with parameters constrained equal across race/ethnicity showed adequate fit suggesting associations were comparable across groups. CONCLUSION: Our study extends the literature by demonstrating the importance of neighborhood perceptions as correlates of BMI across race/ethnicity, and highlights the role of psychological and physiological pathways.

Reactivation of Latent Epstein-Barr Virus: A Comparison after Exposure to Gamma, Proton, Carbon, and Iron Radiation.

Among the many stressors astronauts are exposed to during spaceflight, cosmic radiation may lead to various serious health effects. Specifically, space radiation may contribute to decreased immunity, which has been documented in astronauts during short- and long-duration missions, as evidenced by several changes in cellular immunity and plasma cytokine levels. Reactivation of latent herpes viruses, either directly from radiation of latently infected cells and/or from perturbation of the immune system, may result in disease in astronauts. Epstein‒Barr virus (EBV) is one of the eight human herpes viruses known to infect more than 90% of human adults and persists for the life of the host without normally causing adverse effects. Reactivation of several latent viruses in astronauts is well documented, although the mechanism of reactivation is not well understood. We studied the effect of four different types of radiation, (1) 137Cs gamma rays, (2) 150-MeV protons, (3) 600 MeV/n carbon ions, and (4) 600 MeV/n iron ions on the activation of lytic gene transcription and of reactivation of EBV in a latently infected cell line (Akata) at doses of 0.1, 0.5, 1.0, and 2.0 Gy. The data showed that for all doses used in this study, lytic gene transcription was induced and median viral loads were significantly higher for all types of radiation than in corresponding control samples, with the increases detected as early as four days post-exposure and generally tapering off at later time points. The viability and size of EBV-infected Akata cells were highly variable and exhibited approximately the same trend in time for all radiation types at 0.1, 0.5, 1.0, and 2.0 Gy. This work shows that reactivation of viruses can occur due to the effect of different types of radiation on latently infected cells in the absence of changes or cytokines produced in the immune system. In general, gamma rays are more effective than protons, carbon ions, and iron ions in inducing latent virus reactivation, though these high-energy particles did induce more sustained and later reactivation of EBV lytic gene transcription. These findings also challenge the common relative biological effectiveness concept that is often used in radiobiology for other end points.

Objectively Measured Social Integration Is Associated With an Immune Risk Phenotype Following Marital Separation.

Background: Close relationships play an integral role in human development, and robust evidence links marital separation and divorce to poor health outcomes. Social integration may play a key role in this association. In many ways, the study of marital separation and divorce provides an ideal model system for a more complete understanding of the association between life stress and physical health. Purpose: The current study investigated associations among objectively measured social integration, psychological distress, and biomarkers of immune health in recently separated adults (N = 49). Methods: We collected four measures of immune functioning-interleukin-6, C-reactive protein, and antibody titers to latent cytomegalovirus and Epstein-Barr virus-that were combined to yield a viral-Immune Risk Profile. To assess how variability in social integration is associated with immunological correlates following the end of a marriage, we incorporated observational ecological momentary assessment data using a novel methodology (the Electronically Activated Recorder). Results: We found that objectively measured social behaviors are associated with concurrent viral-Immune Risk Profile scores over and above the effects of psychological distress and that psychological distress may be linked to biomarkers of immune health through social integration. Conclusions: This research expands current knowledge of biomarkers of immune health after divorce and separation and includes a new methodology for objective measures of social engagement.

An Evaluation of Perceived Health Risk and Depressive Symptoms Before a Disaster in Predicting Postdisaster Inflammation.

OBJECTIVE: Exposure to major life stressors is associated with subsequent enhanced inflammation-related disease processes. Depressive symptoms exacerbate stress-induced inflammatory responses. Moreover, those who report a high degree of perceived health risk before being exposed to a major life stressor such as a disaster are at risk for poor health outcomes. The present study examined whether perceived health risk and depressive symptoms before a disaster were associated with postdisaster inflammation markers. METHODS: The sample included 124 participants (mean [standard deviation] age = 55 [16] years; 69% women). At a baseline visit, participants completed self-report measures of perceived health risk and depressive symptoms (Center for Epidemiologic Studies Depression Scale) in addition to a blood draw for the assessment of inflammation markers (C-reactive protein, tumor necrosis factor receptor 1, and interleukin 6). All participants lived near a large petrochemical complex where an unexpected explosion occurred. A second blood sample was obtained 2 to 6 months after the explosion. RESULTS: No significant differences in inflammation markers were found between predisaster and postdisaster assessment (p > .21). An interaction between predisaster perceived health risk and depressive symptoms in predicting postdisaster circulating inflammation markers was identified (Cohen f = 0.051). Specifically, predisaster perceived health risk was associated with postdisaster circulating inflammation markers if predisaster depressive symptoms were greater than 8.10 on the Center for Epidemiologic Studies Depression Scale. CONCLUSIONS: These findings add to our understanding of the complex interactions between stress, depression, and immune responses. Indeed, findings provide a potential mechanism (i.e., inflammation) explaining the association between exposure to major life stressors and negative mental and physical health outcomes.

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences.

BACKGROUND: Adolescent females have a higher prevalence of depression in comparison to their male peers - a disparity that has been increasing over the past decade. Depression is of concern as it is associated with chronic disease and to immune dysregulation, which may be one mechanism linking depression to future pathology. This study examined the extent to which sex moderated the association between depressive symptoms and immune dysregulation during adolescence using Epstein-Barr virus (EBV) reactivation, a biomarker of cellular immune response, as a model. METHODS: A representative community sample of 259 female and 279 male adolescents aged 11-17 years who were EBV IgG positive were examined. Trained interviewers collected the data during two home visits, one week apart. Depressive symptoms were measured at the first visit using the 9 item short-form of the Center for Epidemiologic Studies-Depression scale. EBV biomarkers were collected via saliva at the second visit and included a qualitative measure of EBV viral capsid antigen immunoglobulin G to assess prior EBV infection and a quantitative measure of EBV DNA to assess the number of viral copies shed in the saliva. RESULTS: In multivariable logistic regression analyses, increasing depressive symptoms were significantly associated with salivary shedding of EBV DNA for adolescent females only (logit=0.66, se=0.30, p<0.05), and the interaction between sex and depressive symptoms on salivary shedding of EBV DNA was statistically significant (logit=-1.19, se=0.42, p<0.01). Sensitivity analyses were conducted in which sex was examined as a moderator in the relationship between depressive symptoms and salivary EBV DNA quantitative copies via Tobit regression; results were consistent with the presented findings. CONCLUSIONS: Depressive symptoms are associated with EBV reactivation among EBV positive female adolescents, but not males. Future research is needed to examine EBV reactivation in female adolescents as a mechanism linking depression to future chronic disease and the role of sex hormones in explaining sex differences in the relationship between depressive symptoms and EBV reactivation.

Peripheral immune system suppression in early abstinent alcohol-dependent individuals: Links to stress and cue-related craving.

BACKGROUND: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. METHODS: A total of 39 early abstinent, treatment-seeking, alcohol-dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. RESULTS: The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also showed a dampened TNFα and TNFR1 response to stress and cue, respectively, and a generalized suppression of IL-6. In the alcohol group, these immune system adaptations occurred alongside significant elevations in anxiety, negative mood and alcohol craving. CONCLUSIONS: Findings demonstrate that broad immunosuppression is still observed in alcohol-dependent individuals after 3 weeks of abstinence and may be linked to motivation for alcohol.

Telomere Length and Neighborhood Circumstances: Evaluating Biological Response to Unfavorable Exposures.

Background: Multilevel frameworks suggest neighborhood circumstances influence biology; however, this relationship is not well studied. Telomere length (TL) shortening has been associated with individual-level and neighborhood-level exposures and disease and may provide insights into underlying biologic mechanisms linking neighborhood with biology. To support neighborhood-biology investigations, we sought to determine the independent effect of neighborhood exposures on TL using standard multilevel linear regression models and quantile regression, a nonlinear, social science method applicable for testing the biologic hypothesis that extremes of the TL distribution are related to poor outcomes.Methods: In a multicenter, cross-sectional study, blood TL was measured in 1,488 individuals from 127 census tracts in three U.S. regions using terminal restriction fragment assays. Multilevel linear and quantile regression models were adjusted for individual-level race, education, perceived stress, and depression. Neighborhood exposures included population density, urban/residential crowding, residential stability/mobility, and socioeconomic status.Results: TL was not associated with any neighborhood variable using linear models, but quantile regression revealed inverse associations between population density and urban crowding at the lower tails of the TL distribution [5th (population density P = 0.03; urban crowding P = 0.002), 50th (both P < 0.001), 75th percentiles (both P < 0.001)]. TL was related to residential stability at the upper tail (95th percentile P = 0.006).Conclusions: Findings support the use of nonlinear statistical methods in TL research and suggest that neighborhood exposures can result in biological effects.Impact: TL may serve as an underlying example of a biologic mechanism that can link neighborhood with biology, thus supporting multilevel investigations in future studies. Cancer Epidemiol Biomarkers Prev; 26(4); 553-60. ©2017 AACRSee all the articles in this CEBP Focus section, "Geospatial Approaches to Cancer Control and Population Sciences."

An ELISA method to compute endpoint titers to Epstein-Barr virus and cytomegalovirus: application to population-based studies.

Indirect fluorescence analysis (IFA), the gold standard for determining herpesvirus antibody titers, is labor-intensive and poorly suited for large population-based studies. The enzyme-linked immunosorbent assay (ELISA) is used widely for measuring antiviral antibodies but also suffers drawbacks such as reduced specificity and the qualitative nature of the results due to limited interpretation of the optical density (OD) units. This paper describes a method to titer herpesvirus antibodies using microplates coated with virally-infected cells in which a standard curve, derived from IFA-scored samples, allowed OD units to be converted into titers. A LOOKUP function was created in order to report the data as traditional IFA-based (i.e., 2-fold) titers. The modified ELISA correlated significantly with IFA and was subsequently used to compute endpoint antibody titers to Epstein-Barr virus (EBV)-virus capsid antigen (VCA) and cytomegalovirus (CMV) in blood samples taken from 398 pregnant Hispanic women. Four women were EBV negative (1%), while 58 women were CMV negative (14.6%). EBV VCA antibody titers were significantly higher than CMV antibody titers (p<0.001). This method allows titering of herpesvirus antibodies by ELISA suitable for large population-based studies. In addition, the LOOKUP table enables conversion from OD-derived titers into 2-fold titers for comparison of results with other studies.

Racial-ethnic differences in Epstein-Barr virus antibody titers among U.S. children and adolescents.

PURPOSE: To examine racial-ethnic differences in Epstein-Barr virus (EBV) antibody levels among U.S. children and adolescents. Elevated titers among seropositive youth can indicate viral reactivation-an indirect measure of impaired cell-mediated immunity. METHODS: Data from the 2003-2010 National Health and Nutrition Examination Survey were analyzed using multivariable linear regression accounting for the complex survey design and potential confounders. The sample comprised 4663 black-African American, Mexican American, and white youth aged 6-17 years who were EBV seropositive. RESULTS: EBV antibody levels were significantly higher for black-African American youth compared with their white peers (b = 0.343, P < .0001). Gender-stratified models were consistent with the total sample except differences in EBV antibody levels were greater between black-African American and white males (b = 0.525, P < .0001) than between black-African American and white females (b = 0.169, P = .0185). Differences in EBV antibody levels between Mexican American and white youth were only marginally significant in the total and the gender-stratified samples. CONCLUSIONS: Black-white differences in EBV antibody levels were found suggesting EBV reactivation and potential disparities in immune function among minority youth. Research on multilevel factors contributing to the disparities is needed, including potential health implications over the life course for minority youth.

Characterization of Epstein-Barr virus reactivation in a modeled spaceflight system.

Epstein-Barr virus (EBV) is the causative agent of mononucleosis and is also associated with several malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma, among others. EBV reactivates during spaceflight, with EBV shedding in saliva increasing to levels ten times those observed pre-and post-flight. Although stress has been shown to increase reactivation of EBV, other factors such as radiation and microgravity have been hypothesized to contribute to reactivation in space. We used a modeled spaceflight environment to evaluate the influence of radiation and microgravity on EBV reactivation. BJAB (EBV-negative) and Raji (EBV-positive) cell lines were assessed for viability/apoptosis, viral antigen and reactive oxygen species expression, and DNA damage and repair. EBV-infected cells did not experience decreased viability and increased apoptosis due to modeled spaceflight, whereas an EBV-negative cell line did, suggesting that EBV infection provided protection against apoptosis and cell death. Radiation was the major contributor to EBV ZEBRA upregulation. Combining modeled microgravity and radiation increased DNA damage and reactive oxygen species while modeled microgravity alone decreased DNA repair in Raji cells. Additionally, EBV-infected cells had increased DNA damage compared to EBV-negative cells. Since EBV-infected cells do not undergo apoptosis as readily as uninfected cells, it is possible that virus-infected cells in EBV seropositive individuals may have an increased risk to accumulate DNA damage during spaceflight. More studies are warranted to investigate this possibility.

Immune system dysregulation occurs during short duration spaceflight on board the space shuttle.

BACKGROUND: Post-flight data suggests immunity is dysregulated immediately following spaceflight, however this data may be influenced by the stress effects of high-G entry and readaptation to terrestrial gravity. It is unknown if immunity is altered during spaceflight. METHODS: Blood samples were collected from 19 US Astronauts onboard the Space Shuttle ~24 h prior to landing and returned for terrestrial analysis. Assays consisted of leukocyte distribution, T cell blastogenesis and cytokine production profiles. RESULTS: Most bulk leukocyte subsets (WBC, differential, lymphocyte subsets) were unaltered during spaceflight, but were altered following landing. CD8+ T cell subsets, including cytotoxic, central memory and senescent were altered during spaceflight. T cell early blastogenesis varied by culture mitogen. Functional responses to staphylococcal enterotoxin were reduced during and following spaceflight, whereas response to anti-CD3/28 antibodies was elevated post-flight. The level of virus specific T cells were generally unaltered, however virus specific T cell function was depressed both during and following flight. Plasma levels of IFNα, IFNγ, IL-1ß, IL-4, IL-10, IL-12, and TNFα were significantly elevated in-flight, while IL-6 was significantly elevated at R + 0. Cytokine production profiles following mitogenic stimulation were significantly altered both during, and following spaceflight. Specifically, production of IFNγ, IL-17 and IL-10 were reduced, but production of TNFα and IL-8 were elevated during spaceflight. CONCLUSIONS: This study indicates that specific parameters among leukocyte distribution, T cell function and cytokine production profiles are altered during flight. These findings distinguish in-flight dysregulation from stress-related alterations observed immediately following landing.

Reactivation of herpes simplex virus type 1 is associated with cytomegalovirus and age.

Recent studies have shown that cytomegalovirus (CMV) may be an emerging marker of immunosenescence. CMV can affect the immune system by directly infecting leukocytes and hematopoietic cells or by eliciting an expansion of oligoclonal CD8+ T cells/contraction of the naïve T cell compartment that may reduce the host's ability to fight other pathogens. To investigate further CMV-associated changes in immunity, a study was conducted with 1,454 adults (ages 25-91) to determine the association between CMV and reactivation of another latent herpesvirus, Herpes simplex virus type 1 (HSV-1), as indexed by antibody titers. Elevated antibody titers to latent HSV-1 were significantly associated with both CMV seropositivity and high CMV antibody levels. Evaluation by specific age groups (<45, 45-64, and 65+ years old) revealed that this association was detectable early in life (<45 years of age). Increases in HSV-1 antibodies by age occurred in CMV seropositive individuals but not CMV seronegative subjects. Within CMV seropositive subjects, increases in HSV-1 antibodies by age were only found in individuals with low CMV antibody levels as those with high CMV antibodies already exhibited elevated HSV-1 antibodies. These associations remained significant after accounting for body mass index, gender, and socioeconomic status. These results suggest that CMV can influence the immune response to another pathogen and support the concept that CMV may accelerate immunosenescence.