Evidence for the Role of Epstein Barr Virus Infections in the Pathogenesis of Acute Coronary Events

Binkley, Philip F.; Cooke, Glen E.; Lesinski, Amanda; Taylor, Mackenzie; Chen, Min; Laskowski, Bryon; Waldman, W. James; Ariza, Maria E.; Williams, Marshall V.; Knight, Deborah; Glaser, Ronald

doi:10.1371/journal.pone.0054008

Cited by 30 publications

(31 citation statements)

References 44 publications

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“…[ [21][22][23] The pathophysiology of EBV reactivation remains uncertain. Recent data suggest that EBV could trigger inflammatory process through interleukin-6 modulation.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus reactivation in critically ill immunocompetent patients

et al. 2015

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O ver the past years, particular attention has been given to herpes virus reactivations among immunocompetent critically ill patients. Although the true pathogenicity of these reactivations is still debated, some authors have hypothesized that it could be related to specific immune failure caused by sepsis or multi-organ failure. Others have argued that it is only a marker of severity. There is increasing evidence that reactivation of cytomegalovirus (CMV) and herpes simplex virus (HSV) is associated with mortality or morbidity, mainly for ventilator-acquired pneumonia. [1,2] CMV seroprevalence ranges from 40% to 95% depending on several factors, including age and geographic area. HSV1 seroprevalence is around 65% among the French population. Epstein-Barr virus (EBV) reactivation has been well docu- Original Article Epstein-Barr Virus Reactivation in Critically IllImmunocompetent Patients Background: Herpes viruses can be reactivated among immunocompetent patients in intensive care unit (ICU). Cytomegalovirus (CMV) and herpes simplex virus (HSV) have been the most studied. We hypothesized that Epstein-Barr virus (EBV) could also be reactivated in immunocompetent patients during their stay in ICU and that this would be associated with morbidity and mortality. Methods:This prospective observational study included 90 patients with an ICU stay of ≥ 5 days. CMV and HSV were considered when clinically suspected and DNA was researched in blood or bronchoalveolar lavage (BAL). EBV DNA viral quantification was performed in the blood samples. Results:EBV DNA was detected in blood of 61 patients (median length for positivity of 7.5 days). CMV DNA was detected in blood of 16 patients (median length for positivity of 13.5 days) and BAL of 6 patients. HSV1 DNA was detected in the BAL of 28 patients (median length for positivity of 7.5 days). Nineteen patients had no viral reactivation, 1 experienced only CMV, 32 had only EBV, 5 had only HSV, 6 had EBV and CMV, 14 had EBV and HSV, and 9 patients reactivated three viruses. Mortality was higher among patients with EBV reactivation (33/61 vs. 7/25, p = 0.02). Length of stay (21 vs. 10 days, p < 0.001) and length of mechanical ventilation (15 vs. 7 days, p < 0.001) were higher among patients with EBV reactivation. Conclusions: This study shows that EBV DNA is detected in blood of diverse ICU patients with ≥ ≥ 5 days of stay and that it is associated with morbidity and mortality. Larger dynamic prospective studies are needed to correlate viral reactivation with immune system evolution during ICU stay and to determine the role of polyviral reactivations. (Biomed J 2015;38:70-76)

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“…[ [21][22][23] The pathophysiology of EBV reactivation remains uncertain. Recent data suggest that EBV could trigger inflammatory process through interleukin-6 modulation.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus reactivation in critically ill immunocompetent patients

et al. 2015

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“…This appears to be mediated at least in part by chronic immune activation caused by HIV, even after suppressing the virus with antiretroviral therapy [ 21 ]. Infections due to hepatitis B virus [ 22 ], hepatitis C [ 23 ], Epstein Barr virus [ 24 , 25 ], cytomegalovirus (CMV) [ 26 , 27 ] and periodontal bacteria [ 28 ] have also been associated with atherosclerosis and CVD through chronic systemic inflammation and other mechanisms. Notably, most of the pathogens implicated in CVD pathogenesis are intracellular organisms and/or may be able to establish chronic or latent infection in humans [ 29 ].…”

Section: Reviewmentioning

confidence: 99%

Tuberculosis and cardiovascular disease: linking the epidemics

Huamán

Henson

Ticona

et al. 2015

Trop Dis Travel Med Vaccines

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The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, subsets of mycobacteria actively replicate during latent tuberculosis infection (LTBI), and recent studies suggest that LTBI is associated with persistent chronic inflammation that may lead to CVD. Recent epidemiologic work has shown that the risk of CVD in persons who develop tuberculosis is higher than in persons without a history of tuberculosis, even several years after recovery from tuberculosis. Together, these data suggest that tuberculosis may play a role in the pathogenesis of CVD. Further research to investigate a potential link between tuberculosis and CVD is warranted.

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“…Epstein-Barr was the first virus to be linked to cancer, and has been linked to nearly all cases of nasopharyngeal carcinoma and important subsets of Burkitt lymphomas, other non-Hodgkins lymphoma and gastric cancer [5], [6], [7], [8]. EBV infection or reactivation has also been associated with lupus [9], multiple sclerosis [10], and cardiovascular disease[11].…”

Section: Introductionmentioning

confidence: 99%

Seroprevalence of Epstein-Barr Virus Infection in U.S. Children Ages 6-19, 2003-2010

et al. 2013

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BackgroundEpstein-Barr virus (EBV) is a common herpesvirus linked to infectious mononucleosis and multiple cancers. There are no national estimates of EBV seroprevalence in the United States. Our objective was to estimate the overall prevalence and sociodemographic predictors of EBV among U.S. children and adolescents aged 6–19.MethodsWe calculated prevalence estimates and prevalence ratios for EBV seroprevalence using data from the 2003–2010 U.S. National Health and Nutrition Examination Survey (NHANES) for children aged 6–19 (n = 8417). Poisson regression was used to calculate multivariable-adjusted prevalence ratios across subgroup categories (sex, race/ethnicity, parental education, household income, household size, foreign-born, BMI, and household smoking).FindingsOverall EBV seroprevalence was 66.5% (95% CI 64.3%–68.7%.). Seroprevalence increased with age, ranging from 54.1% (95% CI 50.2%–57.9%) for 6–8 year olds to 82.9% (95% CI 80.0%–85.9%) for 18–19 year olds. Females had slightly higher seroprevalence (68.9%, 95% CI 66.3%–71.6%) compared to males (64.2%, 95% CI 61.7%–66.8%). Seroprevalence was substantially higher for Mexican-Americans (85.4%, 95% CI 83.1%–87.8%) and Non-Hispanic Blacks (83.1%, 95% CI 81.1%–85.1%) than Non-Hispanic Whites (56.9%, 95% CI 54.1%–59.8%). Large differences were also seen by family income, with children in the lowest income quartile having 81.0% (95% CI 77.6%–84.5%) seroprevalence compared to 53.9% (95% CI 50.5%–57.3%) in the highest income quartile, with similar results for parental education level. These results were not explained by household size, BMI, or parental smoking. Among those who were seropositive, EBV antibody titers were significantly higher for females, Non-Hispanic Blacks and Mexican-Americans, with no association found for socioeconomic factors.ConclusionsIn the first nationally representative U.S. estimates, we found substantial socioeconomic and race/ethnic differences in the seroprevalence of EBV across all ages for U.S. children and adolescents. These estimates can help researchers and clinicians identify groups most at risk, inform research on EBV-cancer etiology, and motivate potential vaccine development.

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Evidence for the Role of Epstein Barr Virus Infections in the Pathogenesis of Acute Coronary Events

Cited by 30 publications

References 44 publications

Epstein-Barr virus reactivation in critically ill immunocompetent patients

Epstein-Barr virus reactivation in critically ill immunocompetent patients

Tuberculosis and cardiovascular disease: linking the epidemics

Seroprevalence of Epstein-Barr Virus Infection in U.S. Children Ages 6-19, 2003-2010

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