title: Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.
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.
authors: Medical Research Council Laboratories, Fajara, The Gambia; School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.
authors: Shamanthi
authors: S
authors: Jayasooriya
authors: Medical Research Council Laboratories, Fajara, The Gambia; Department of Infection and Immunity, The University of Sheffield Medical School, Sheffield, United Kingdom; The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
authors: Thushan I
authors: TI
authors: de Silva
authors: Medical Research Council Laboratories, Fajara, The Gambia.
authors: Jainaba
authors: J
authors: Njie-jobe
authors: Medical Research Council Laboratories, Fajara, The Gambia.
authors: Chilel
authors: C
authors: Sanyang
authors: School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.
authors: Alison M
authors: AM
authors: Leese
authors: School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.
authors: Andrew I
authors: AI
authors: Bell
authors: MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors: Karen A
authors: KA
authors: McAulay
authors: The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
authors: Peng
authors: P
authors: Yanchun
authors: School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.
authors: Heather M
authors: HM
authors: Long
authors: The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
authors: Tao
authors: T
authors: Dong
authors: Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Hilton C
authors: HC
authors: Whittle
authors: School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.
authors: Alan B
authors: AB
authors: Rickinson
authors: Nuffied Department of Medicine, NDM Research Building, University of Oxford, Old Road Campus, Headington, United Kingdom.
authors: Sarah L
authors: SL
authors: Rowland-Jones
authors: School of Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.
authors: Andrew D
authors: AD
authors: Hislop
authors: Medical Research Council Laboratories, Fajara, The Gambia; Department of Immunology, Monash University, Commercial Road, Prahran, Melbourne, Victoria, Australia.
authors: Katie L
authors: KL
authors: Flanagan
mesh_terms: D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D005714:Gambia / Q000453:epidemiology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D007223:Infant; D018655:Lymphocyte Count; D008297:Male
chemical_list: D000914:Antibodies, Viral; D007075:Immunoglobulin M