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Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.

Jayasooriya S, de Silva TI, Njie-jobe J, Sanyang C, Leese AM, Bell AI, McAulay KA, Yanchun P, Long HM, Dong T, Whittle HC, Rickinson AB, Rowland-Jones SL, Hislop AD, Flanagan KL - PLoS Pathog. (2015)

Bottom Line: In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells.That response was culled and the cells lost activation markers over time, just as seen in AIM.However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Laboratories, Fajara, The Gambia; School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.

ABSTRACT
Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14-18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms.

No MeSH data available.


Related in: MedlinePlus

EBV loads in peripheral blood mononuclear cells (PBMCs) from Gambian infants compared to Acute Infectious Mononuclear (AIM) patients.EBV genome loads in IgM-IgG+ Gambian children at visit one (n = 70) and after six months at visit four (n = 58), compared to IgM+IgG+/- children from either time point. For comparison, data of virus loads measured in Caucasian adolescent AIM patients are also presented. The dashed line represents the lower limit of detection for EBV genomes in the assay. Donors below the dashed line had undetectable viral loads. P values calculated using Dunn’s Multiple Comparison Test (one way analysis of variance (ANOVA)). * p<0.05 ** P<0.01 *** P<0.001
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ppat.1004746.g002: EBV loads in peripheral blood mononuclear cells (PBMCs) from Gambian infants compared to Acute Infectious Mononuclear (AIM) patients.EBV genome loads in IgM-IgG+ Gambian children at visit one (n = 70) and after six months at visit four (n = 58), compared to IgM+IgG+/- children from either time point. For comparison, data of virus loads measured in Caucasian adolescent AIM patients are also presented. The dashed line represents the lower limit of detection for EBV genomes in the assay. Donors below the dashed line had undetectable viral loads. P values calculated using Dunn’s Multiple Comparison Test (one way analysis of variance (ANOVA)). * p<0.05 ** P<0.01 *** P<0.001

Mentions: Since acquisition of EBV in similar African cohorts begins between six and twelve months after birth [29,30], it is likely that at least some children who were IgG reactive to VCA within the cohort were infected with EBV within the last six months prior to recruitment. To examine for evidence of recent infection among these donors, EBV genome loads in PBMCs were measured by qPCR analysis. Fig. 2 shows viral genome load data from PBMCs collected from 70 IgM−IgG+ donors at baseline, 58 of these donors six months later, and six very recently infected IgM VCA reactive donors (some of whom also had VCA-specific IgG antibodies). Genome load data from Caucasian adolescent patients undergoing primary symptomatic EBV infection, AIM, assessed using the same qPCR assay are also included for comparison.


Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.

Jayasooriya S, de Silva TI, Njie-jobe J, Sanyang C, Leese AM, Bell AI, McAulay KA, Yanchun P, Long HM, Dong T, Whittle HC, Rickinson AB, Rowland-Jones SL, Hislop AD, Flanagan KL - PLoS Pathog. (2015)

EBV loads in peripheral blood mononuclear cells (PBMCs) from Gambian infants compared to Acute Infectious Mononuclear (AIM) patients.EBV genome loads in IgM-IgG+ Gambian children at visit one (n = 70) and after six months at visit four (n = 58), compared to IgM+IgG+/- children from either time point. For comparison, data of virus loads measured in Caucasian adolescent AIM patients are also presented. The dashed line represents the lower limit of detection for EBV genomes in the assay. Donors below the dashed line had undetectable viral loads. P values calculated using Dunn’s Multiple Comparison Test (one way analysis of variance (ANOVA)). * p<0.05 ** P<0.01 *** P<0.001
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376400&req=5

ppat.1004746.g002: EBV loads in peripheral blood mononuclear cells (PBMCs) from Gambian infants compared to Acute Infectious Mononuclear (AIM) patients.EBV genome loads in IgM-IgG+ Gambian children at visit one (n = 70) and after six months at visit four (n = 58), compared to IgM+IgG+/- children from either time point. For comparison, data of virus loads measured in Caucasian adolescent AIM patients are also presented. The dashed line represents the lower limit of detection for EBV genomes in the assay. Donors below the dashed line had undetectable viral loads. P values calculated using Dunn’s Multiple Comparison Test (one way analysis of variance (ANOVA)). * p<0.05 ** P<0.01 *** P<0.001
Mentions: Since acquisition of EBV in similar African cohorts begins between six and twelve months after birth [29,30], it is likely that at least some children who were IgG reactive to VCA within the cohort were infected with EBV within the last six months prior to recruitment. To examine for evidence of recent infection among these donors, EBV genome loads in PBMCs were measured by qPCR analysis. Fig. 2 shows viral genome load data from PBMCs collected from 70 IgM−IgG+ donors at baseline, 58 of these donors six months later, and six very recently infected IgM VCA reactive donors (some of whom also had VCA-specific IgG antibodies). Genome load data from Caucasian adolescent patients undergoing primary symptomatic EBV infection, AIM, assessed using the same qPCR assay are also included for comparison.

Bottom Line: In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells.That response was culled and the cells lost activation markers over time, just as seen in AIM.However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Laboratories, Fajara, The Gambia; School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.

ABSTRACT
Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14-18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms.

No MeSH data available.


Related in: MedlinePlus