Holoendemic malaria exposure is associated with altered Epstein-Barr virus-specific CD8(+) T-cell differentiation
Authors
Chattopadhyay, Pratip K.Chelimo, Kiprotich
Embury, Paula B.
Mulama, David H.
Sumba, Peter Odada
Gostick, Emma
Ladell, Kristin
Brodie, Tess M.
Vulule, John
Roederer, Mario
Moormann, Ann M.
Price, David A.
Document Type
Journal ArticlePublication Date
2013-02-01Keywords
AfricaCD8-Positive T-Lymphocytes
Child
Child, Preschool
Coinfection
Epstein-Barr Virus Infections
Flow Cytometry
Herpesvirus 4, Human
Humans
Infant
Malaria, Falciparum
Plasmodium falciparum
T-Lymphocyte Subsets
International Public Health
Oncology
Pediatrics
Virus Diseases
Metadata
Show full item recordAbstract
Coinfection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) is a major risk factor for endemic Burkitt lymphoma (eBL), still one of the most prevalent pediatric cancers in equatorial Africa. Although malaria infection has been associated with immunosuppression, the precise mechanisms that contribute to EBV-associated lymphomagenesis remain unclear. In this study, we used polychromatic flow cytometry to characterize CD8(+) T-cell subsets specific for EBV-derived lytic (BMFL1 and BRLF1) and latent (LMP1, LMP2, and EBNA3C) antigens in individuals with divergent malaria exposure. No malaria-associated differences in EBV-specific CD8(+) T-cell frequencies were observed. However, based on a multidimensional analysis of CD45RO, CD27, CCR7, CD127, CD57, and PD-1 expression, we found that individuals living in regions with intense and perennial (holoendemic) malaria transmission harbored more differentiated EBV-specific CD8(+) T-cell populations that contained fewer central memory cells than individuals living in regions with little or no (hypoendemic) malaria. This profile shift was most marked for EBV-specific CD8(+) T-cell populations that targeted latent antigens. Importantly, malaria exposure did not skew the phenotypic properties of either cytomegalovirus (CMV)-specific CD8(+) T cells or the global CD8(+) memory T-cell pool. These observations define a malaria-associated aberration localized to the EBV-specific CD8(+) T-cell compartment that illuminates the etiology of eBL.Source
J Virol. 2013 Feb;87(3):1779-88. doi: 10.1128/JVI.02158-12. Epub 2012 Nov 21. Link to article on publisher's siteDOI
10.1128/JVI.02158-12Permanent Link to this Item
http://hdl.handle.net/20.500.14038/46640PubMed ID
23175378Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/JVI.02158-12