Behavioral, Virologic, and Immunologic Factors Associated With Acquisition and Severity of Primary Epstein-Barr Virus Infection in University Students

ArticleinThe Journal of Infectious Diseases 207(1) · October 2012with7 Reads
DOI: 10.1093/infdis/jis646 · Source: PubMed
Abstract
Background: University students were studied prospectively to determine the incidence of and risk factors for acquisition of primary Epstein-Barr virus (EBV) infection and the virologic and immune correlates of disease severity. Methods: EBV antibody-negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by polymerase chain reaction. Lymphocyte and natural killer (NK) cell numbers and activation were measured by flow cytometry, and plasma cytokine levels were measured by a multiplex assay. Results: Of 546 students screened, 202 (37%) were antibody negative; 143 antibody-negative students were enrolled. During a median of 3 years of observation, 66 subjects experienced primary infection. Of these, 77% had infectious mononucleosis, 12% had atypical symptoms, and 11% were asymptomatic. Subjects reporting deep kissing with or without coitus had the same higher risk of infection than those reporting no kissing (P < .01). Viremia was transient, but median oral shedding was 175 days. Increases were observed in numbers of NK cells and CD8(+) T-cells but not in numbers of CD4(+) T-cells during acute infection. Severity of illness correlated positively with both blood EBV load (P = .015) and CD8(+) lymphocytosis (P = .0003). Conclusions: Kissing was a significant risk for primary EBV infection. A total of 89% of infections were symptomatic, and blood viral load and CD8(+) lymphocytosis correlated with disease severity.
    • "During the first 5 years after resolution of IM symptoms an increased risk to develop EBV-associated classical Hodgkin lymphoma is observed (Hjalgrim et al., 2003). EBV viremia, possibly driving EBV-specific CD8 + T cell expansion and tumorigenesis, could result from insufficient innate immune control of EBV, and indeed frequencies or counts for the innate lymphocytes natural killer (NK) cells were found to either inversely or directly correlate with EBV titers in infectious mononucleosis (Balfour et al., 2013; Williams et al., 2005). Further arguing for a role of NK cells in EBV-specific immune control, primary immunodeficiencies that affect NK cells or NK cell recognition of EBV-transformed B cells have been reported to be associated with EBV-positive malignancies and high susceptibility to EBV (Eidenschenk et al., 2006; Parolini et al., 2000; Shaw et al., 2012). "
    [Show abstract] [Hide abstract] ABSTRACT: Primary infection with the human oncogenic Epstein-Barr virus (EBV) can result in infectious mononucleosis (IM), a self-limiting disease caused by massive lymphocyte expansion that predisposes for the development of distinct EBV-associated lymphomas. Why some individuals experience this symptomatic primary EBV infection, whereas the majority acquires the virus asymptomatically, remains unclear. Using a mouse model with reconstituted human immune system components, we show that depletion of human natural killer (NK) cells enhances IM symptoms and promotes EBV-associated tumorigenesis mainly because of a loss of immune control over lytic EBV infection. These data suggest that failure of innate immune control by human NK cells augments symptomatic lytic EBV infection, which drives lymphocyte expansion and predisposes for EBV-associated malignancies.
    Article · Aug 2015
    • "Herpesviruses are characterized by lifelong latent infection in the host, where the cells in which they remain latent vary dependent on type of herpesvirus (Roizmann et al., 1992). In humans, the gamma herpesvirus Epstein–Barr virus (EBV) is asymptomatic or causes very mild symptoms if the infection occurs in childhood, whereas infection later in life is associated with mononucleosis (Balfour et al., 2013a). Most reviews indicate that >90% of the adult population in the USA are persistently infected with EBV whereas the antibody prevalence in children is around 50% (Balfour et al., 2013b). "
    [Show abstract] [Hide abstract] ABSTRACT: The equine gamma herpesviruses 2 and 5 (EHV-2 and -5) have frequently been observed in the equine population and until recently presumed low to nonpathogenic. However, recent reports linking presence of equine gamma herpesviruses with clinical signs of mild to severe lung disease, suggest that the role of these viruses in respiratory disease and poor performance syndrome is still unclear. Moreover, baseline data regarding the temporal pattern of shedding of EHV-2 and EHV-5 within stables and within individual actively racing horses have been lacking. In a prospective longitudinal study, we followed elite racing Standardbred trotters at monthly intervals for 13 months, to investigate whether the amount of EHV-2 and EHV-5 shedded in nasal secretions varied over time within and between individual horses. Sixty-six elite horses were investigated by analyzing nasal swabs and serum samples, a health check and evaluation of athletic performance monthly during the study period. Nasal swabs were analyzed with two newly developed qPCR assays for EHV-2 and EHV-5, respectively. Of 663 samples, 197 (30%) were positive for EHV-2 and 492 (74%) positive for EHV-5. Furthermore, 176 (27%) of the samples were positive for both EHV-2 and EHV-5 simultaneously. There was considerable variation in the amount and frequency of shedding of EHV-2 and EHV-5 within and between individual horses. Viral load varied seasonally, but neither EHV-2 nor EHV-5 viral peaks were associated with clinical respiratory disease and/or poor performance in racing Standardbred trotters. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Jun 2015
    • "IM is an acute EBV infection typically presenting with a triad of fever, pharyngitis and lymphadenopathy (LAD), with self-resolution within 1-2 months. In this setting, EBV typically replicates and survives in CD21+ B cells [1] with systemic symptoms attributed to the degree of monoclonal or polyclonal [2] CD8+ cytotoxic T cell response to the viremia [3, 4]. There are rare fulminant infections, typically in immunodeficient patients, most notably due to XLP. "
    [Show abstract] [Hide abstract] ABSTRACT: Epstein Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (EBV-HLH) is a form of acquired, infection-related HLH which typically represents a fulminant presentation of an acute EBV infection of CD8+ T cells with 30-50% mortality rate. Systemic EBV-positive lymphoproliferative disease of childhood (SE-LPD) is a rare T cell lymphoproliferative disorder predominantly arising in the setting of acute EBV infection, often presenting with HLH. Since both entities have been associated with clonal T cell populations, the discrimination between these diseases is often ambiguous. We report a unique case of a 21 years old female who presented with clinical and laboratory findings of florid HLH in the setting of markedly elevated EBV titers (>1 million) and an aberrant T cell population shown to be clonal by flow cytometry, karyotype, and molecular studies. This case raises the differential of EBV-HLH versus SE-LPD. Review of the literature identified 74 cases of reported EBV-HLH and 21 cases of SE-LPD with associated HLH in 25 studies. Of those cases with available outcome data, 62 of 92 cases (67%) were fatal. Of 60 cases in which molecular clonality was demonstrated, 37 (62%) were fatal, while all 14 cases (100%) demonstrating karyotypic abnormalities were fatal. Given the karyotypic findings in this sentinel case, a diagnosis of SE-LPD was rendered. The overlapping clinical and pathologic findings suggest that EBV-HLH and SE-LPD are a biologic continuum, rather than discrete entities. The most clinically useful marker of mortality was an abnormal karyotype rather than other standards of clonality assessment.
    Full-text · Article · Oct 2014
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