Research Article: Aged-associated cytomegalovirus and Epstein-Barr virus reactivation and cytomegalovirus relationship with the frailty syndrome in older women

Date Published: July 10, 2017

Publisher: Public Library of Science

Author(s): Ronaldo Luis Thomasini, Daniele Sirineu Pereira, Fabiana Souza Máximo Pereira, Elvis Cueva Mateo, Thamires Nader Mota, Gabrielle Gontijo Guimarães, Leani Souza Máximo Pereira, Cristiano Xavier Lima, Mauro Martins Teixeira, Antônio Lúcio Teixeira, Michael Nevels.


Immunosenescence is an age-related reduction of immune system activity that can be associated with frailty. This study aimed to compare cytomegalovirus (CMV) and Epstein–Barr virus (EBV) reactivations (based on viremias) between young and elderly women who had a chronic CMV and/or EBV infection (i.e., an IgG+ serostatus) without an acute infection (i.e., an IgM− serostatus), and among the elderly group categorized according to frailty status. DNA was extracted from plasma using standard protocols and serostatus was determined by enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction analyses for CMV and EBV were carried out and viral loads were determined. Among elderly women (n = 71), 59% were positive for CMV, in contrast to only 8% of young women (n = 73). Elderly women classified as frail, pre-frail, and non-frail presented 82%, 56%, and 48% positivity for CMV, respectively. Frequency and viral load were significantly higher in the elderly group vs. the young group (p < 0.0001 and p = 0.01, respectively) and in elderly with frailty vs. those without frailty (p = 0.007 and p = 0.03, respectively). The frequency of CMV reactivation presented odds ratios of 11.77 for aging and 6.13 for frailty, and relative risks of 5.39 for aging and 1.93 for frailty. EBV was detected in 30% of the elderly women and 15% of the young women (p = 0.04); however, the viral load did not significantly differ between the two age groups. The frequency of EBV reactivation presented odds ratios of 2.36 for aging and 2.90 for frailty, and relative risks of 1.96 for aging and 2.12 for frailty. However, no difference in EBV viral load among the frailty status subgroups was found. In conclusion, the frequency of CMV reactivation was associated with aging and ongoing frailty, whereas the frequency of EBV reactivation was associated only with aging.

Partial Text

The process of aging is accompanied by chronic diseases that can be controlled without impairing the independence and autonomy of the individual. However, a significant portion of the elderly population has conditions, constituting ‘frailty’, that render them more vulnerable to harm and increase their risk of experiencing adverse events. The term frailty has been used frequently in the literature, but its precise definition has evolved during recent years. According to Fried [1], frailty is a state of increased vulnerability that is associated with aging and results from a reduced physiological reserve and a decreased ability to maintain homeostasis under stress. It is a multi-systemic and highly prevalent syndrome that affects elderly individuals and can result in serious morbidity and mortality [2,3].

The qPCR assays for CMV and EBV both yielded standard curves with R2 = 0.99. Neither nonspecific amplification nor cross-reaction with other human herpesviruses was found, and the lower bound of sensitivity was 400 viral copies/mL. In the young group (n = 79), 73 individuals (92.4%) were CMV IgG+/IgM− and EBV IgG+/IgM−. Among the remaining individuals, four subjects (5%) were CMV IgG−/EBV IgG−, one (1.2%) was CMV IgG+/EBV IgG−, and another (1.2%) was CMV IgG−/EBV IgG+. No participants were IgM+. In the elderly group (total n = 75; non-frail n = 27; pre-frail n = 24; and frail n = 24), 71 individuals (94.6%) were CMV IgG+/IgM− and EBV IgG+/IgM−, three individuals (4%) were CMV IgG−/EBV IgG−, and only one individual (1.3%) was CMV IgM+. Differences in serostatuses between groups and subgroups were not statistically significant.

Most herpesviruses are ubiquitous and persist in a latent state in their hosts for life. However, some viruses in this family, such as human herpes simplex virus 2 and human herpesvirus 8 (HHV-8 or Kaposi’s sarcoma-associated herpesvirus), are associated with lower seroprevalences than other herpesviruses. Seroprevalence depends on the type of herpesvirus and the age of a host, and can vary geographically. The infection can become reactivated after immunosuppressive therapy and other conditions that affect immune function [15,23]. The clinical outcome of viral reactivation depends on the type of disease, severity of immunosuppression, and clinical baseline of the subjects. However, severe immunosuppression is not a sine qua non condition for herpesviral reactivation, and viral reactivation can be asymptomatic, especially in cases with low viral loads [17,24,25].




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