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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 VCA serological status of Gambian children.Serological status of study participants at baseline (visit one) and six months later at visit four.
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ppat.1004746.g001: EBV VCA serological status of Gambian children.Serological status of study participants at baseline (visit one) and six months later at visit four.

Mentions: Initially children were tested for their EBV-VCA antibody status and categorised into one of three groups: non-infected (IgM−IgG−), established infection (IgM−IgG+) or very recently infected (IgM+IgG+/−). At visit one, 71 children had established EBV infection as judged by the presence of VCA-specific antibodies of IgG but not IgM class (Fig. 1). Another four children showed evidence of recent infection, with three having IgM VCA-specific antibodies only and one having both IgM and IgG VCA-specific antibodies. The remaining 39 children appeared to be non-infected, having no detectable VCA-specific antibodies or viral genomes in their peripheral blood mononuclear cells (PBMCs). At visit four (six months later) 17 of these 39 initially EBV non-infected donors had become VCA IgM−IgG+, another two had become VCA IgM+IgG+, 13 remained VCA IgM−IgG−, while seven dropped out of the study. The four initially IgM+ children had now become IgM- and had developed VCA-specific IgG. All children, including those with VCA-specific IgM antibodies, were asymptomatic for classical symptoms of AIM (fever, lymphadenopathy, malaise) prior to recruitment and at subsequent visits, based on maternal history and clinical evaluation. Overall, 62% of children showed serological evidence of being EBV infected at baseline, rising to 86% among those remaining in the study six months later. An analysis of VCA IgG titre in a subset of 25 pairs of samples from children at visit one and four showed no significant difference in titre (p = 0.774, S1A Fig).


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 VCA serological status of Gambian children.Serological status of study participants at baseline (visit one) and six months later at visit four.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1004746.g001: EBV VCA serological status of Gambian children.Serological status of study participants at baseline (visit one) and six months later at visit four.
Mentions: Initially children were tested for their EBV-VCA antibody status and categorised into one of three groups: non-infected (IgM−IgG−), established infection (IgM−IgG+) or very recently infected (IgM+IgG+/−). At visit one, 71 children had established EBV infection as judged by the presence of VCA-specific antibodies of IgG but not IgM class (Fig. 1). Another four children showed evidence of recent infection, with three having IgM VCA-specific antibodies only and one having both IgM and IgG VCA-specific antibodies. The remaining 39 children appeared to be non-infected, having no detectable VCA-specific antibodies or viral genomes in their peripheral blood mononuclear cells (PBMCs). At visit four (six months later) 17 of these 39 initially EBV non-infected donors had become VCA IgM−IgG+, another two had become VCA IgM+IgG+, 13 remained VCA IgM−IgG−, while seven dropped out of the study. The four initially IgM+ children had now become IgM- and had developed VCA-specific IgG. All children, including those with VCA-specific IgM antibodies, were asymptomatic for classical symptoms of AIM (fever, lymphadenopathy, malaise) prior to recruitment and at subsequent visits, based on maternal history and clinical evaluation. Overall, 62% of children showed serological evidence of being EBV infected at baseline, rising to 86% among those remaining in the study six months later. An analysis of VCA IgG titre in a subset of 25 pairs of samples from children at visit one and four showed no significant difference in titre (p = 0.774, S1A Fig).

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