Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.
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 exp...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-03-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1004746 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850125132099485696 |
|---|---|
| author | Shamanthi Jayasooriya Thushan I de Silva Jainaba Njie-jobe Chilel Sanyang Alison M Leese Andrew I Bell Karen A McAulay Peng Yanchun Heather M Long Tao Dong Hilton C Whittle Alan B Rickinson Sarah L Rowland-Jones Andrew D Hislop Katie L Flanagan |
| author_facet | Shamanthi Jayasooriya Thushan I de Silva Jainaba Njie-jobe Chilel Sanyang Alison M Leese Andrew I Bell Karen A McAulay Peng Yanchun Heather M Long Tao Dong Hilton C Whittle Alan B Rickinson Sarah L Rowland-Jones Andrew D Hislop Katie L Flanagan |
| author_sort | Shamanthi Jayasooriya |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9f7656ff746e49acba6b99d0dc0a6fc4 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2015-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-9f7656ff746e49acba6b99d0dc0a6fc42025-08-20T02:34:10ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-03-01113e100474610.1371/journal.ppat.1004746Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.Shamanthi JayasooriyaThushan I de SilvaJainaba Njie-jobeChilel SanyangAlison M LeeseAndrew I BellKaren A McAulayPeng YanchunHeather M LongTao DongHilton C WhittleAlan B RickinsonSarah L Rowland-JonesAndrew D HislopKatie L FlanaganEpstein-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.https://doi.org/10.1371/journal.ppat.1004746 |
| spellingShingle | Shamanthi Jayasooriya Thushan I de Silva Jainaba Njie-jobe Chilel Sanyang Alison M Leese Andrew I Bell Karen A McAulay Peng Yanchun Heather M Long Tao Dong Hilton C Whittle Alan B Rickinson Sarah L Rowland-Jones Andrew D Hislop Katie L Flanagan Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children. PLoS Pathogens |
| title | Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children. |
| title_full | Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children. |
| title_fullStr | Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children. |
| title_full_unstemmed | Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children. |
| title_short | Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children. |
| title_sort | early virological and immunological events in asymptomatic epstein barr virus infection in african children |
| url | https://doi.org/10.1371/journal.ppat.1004746 |
| work_keys_str_mv | AT shamanthijayasooriya earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT thushanidesilva earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT jainabanjiejobe earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT chilelsanyang earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT alisonmleese earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT andrewibell earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT karenamcaulay earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT pengyanchun earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT heathermlong earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT taodong earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT hiltoncwhittle earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT alanbrickinson earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT sarahlrowlandjones earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT andrewdhislop earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren AT katielflanagan earlyvirologicalandimmunologicaleventsinasymptomaticepsteinbarrvirusinfectioninafricanchildren |