Revisiting the Effect of Acute P. falciparum Malaria on Epstein-Barr Virus: Host Balance in the Setting of Reduced Malaria Endemicity

Shamanthi Jayasooriya,Andrew Hislop,Tao Dong,Michael Walther,Yanchun Peng,Debbie Croom-Carter,Sarah Rowland-Jones,Hilton Whittle,Andrew Bell,Alan Rickinson,Ya Jankey,Alison J Sinclair

doi:10.1371/journal.pone.0031142

Abstract

Burkitt's lymphoma (BL), an EBV-associated tumour, occurs at high incidence in populations where malaria is holoendemic. Previous studies in one such population suggested that acute P.falciparum infection impairs EBV-specific T-cell surveillance, allowing expansion of EBV infected B-cells from which BL derives. We re-examined the situation in the same area, The Gambia, after a reduction in malaria endemicity. Cellular immune responses to EBV were measured in children with uncomplicated malaria before (day 0) and after treatment (day 28), comparing EBV genome loads in blood and EBV-specific CD8+ T-cell numbers (assayed by MHC Class I tetramers and IFNγ ELISPOTS) with those seen in age- and sex-matched healthy controls. No significant changes were seen in EBV genome loads, percentage of EBV-specific CD8+ T-cells and IFNγ producing T-cells in acute versus convalescent samples, nor any difference versus controls. Regression assays performed also no longer detected any impairment of EBV-specific T-cell surveillance. Acute uncomplicated malaria infection no longer alters EBV-specific immune responses in children in The Gambia. Given the recent decline in malaria incidence in that country, we hypothesise that gross disturbance of the EBV-host balance may be a specific effect of acute malaria only in children with a history of chronic/recurrent malaria challenge.

Highlights

EBV is a gamma herpesvirus, ubiquitous in human populations, that is usually acquired early in life by the oral route, replicates locally through a virus productive infection at oropharyngeal sites and is carried thereafter for life as a latent, largely asymptomatic, infection of the B-cell pool [1,2]
A somewhat analogous situation is thought to occur in Africa, where the similar geographic distributions of Burkitt Lymphoma (BL), an EBVassociated childhood tumour, and of holoendemic malaria suggests that malaria may predispose to BL through suppression of T-cell surveillance leading to increased viral loads [7]
We show that the situation currently in The Gambia is different to that reported earlier [8,14], children with acute uncomplicated P.falciparum malaria experience no elevation in EBV genome load in the blood compared to age- and sex-matched healthy controls, nor do they have any evidence of reduction in numbers or impairment of function of their EBV-specific CD8+ T-cells

Summary

Introduction

EBV is a gamma herpesvirus, ubiquitous in human populations, that is usually acquired early in life by the oral route, replicates locally through a virus productive (lytic) infection at oropharyngeal sites and is carried thereafter for life as a latent, largely asymptomatic, infection of the B-cell pool [1,2]. This apparently innocuous agent has potent growth-transforming ability for its principal target cell, the B lymphocyte, and is linked to several B-cell malignancies especially in immunosuppressed hosts [3]. A somewhat analogous situation is thought to occur in Africa, where the similar geographic distributions of Burkitt Lymphoma (BL), an EBVassociated childhood tumour, and of holoendemic malaria suggests that malaria may predispose to BL through suppression of T-cell surveillance leading to increased viral loads [7]

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Results

Conclusion