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A molecular link between malaria and Epstein-Barr virus reactivation.
PLoS Pathog. 2007 Jun; 3(6):e80.PP

Abstract

Although malaria and Epstein-Barr (EBV) infection are recognized cofactors in the genesis of endemic Burkitt lymphoma (BL), their relative contribution is not understood. BL, the most common paediatric cancer in equatorial Africa, is a high-grade B cell lymphoma characterized by c-myc translocation. EBV is a ubiquitous B lymphotropic virus that persists in a latent state after primary infection, and in Africa, most children have sero-converted by 3 y of age. Malaria infection profoundly affects the B cell compartment, inducing polyclonal activation and hyper-gammaglobulinemia. We recently identified the cystein-rich inter-domain region 1alpha (CIDR1alpha) of the Plasmodium falciparum membrane protein 1 as a polyclonal B cell activator that preferentially activates the memory compartment, where EBV is known to persist. Here, we have addressed the mechanisms of interaction between CIDR1alpha and EBV in the context of B cells. We show that CIDR1alpha binds to the EBV-positive B cell line Akata and increases the number of cells switching to the viral lytic cycle as measured by green fluorescent protein (GFP) expression driven by a lytic promoter. The virus production in CIDR1alpha-exposed cultures was directly proportional to the number of GFP-positive Akata cells (lytic EBV) and to the increased expression of the EBV lytic promoter BZLF1. Furthermore, CIDR1alpha stimulated the production of EBV in peripheral blood mononuclear cells derived from healthy donors and children with BL. Our results suggest that P. falciparum antigens such as CIDR1alpha can directly induce EBV reactivation during malaria infection that may increase the risk of BL development for children living in malaria-endemic areas. To our knowledge, this is the first report to show that a microbial protein can drive a latently infected B cell into EBV replication.

Authors+Show Affiliations

Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17559303

Citation

Chêne, Arnaud, et al. "A Molecular Link Between Malaria and Epstein-Barr Virus Reactivation." PLoS Pathogens, vol. 3, no. 6, 2007, pp. e80.
Chêne A, Donati D, Guerreiro-Cacais AO, et al. A molecular link between malaria and Epstein-Barr virus reactivation. PLoS Pathog. 2007;3(6):e80.
Chêne, A., Donati, D., Guerreiro-Cacais, A. O., Levitsky, V., Chen, Q., Falk, K. I., Orem, J., Kironde, F., Wahlgren, M., & Bejarano, M. T. (2007). A molecular link between malaria and Epstein-Barr virus reactivation. PLoS Pathogens, 3(6), e80.
Chêne A, et al. A Molecular Link Between Malaria and Epstein-Barr Virus Reactivation. PLoS Pathog. 2007;3(6):e80. PubMed PMID: 17559303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A molecular link between malaria and Epstein-Barr virus reactivation. AU - Chêne,Arnaud, AU - Donati,Daria, AU - Guerreiro-Cacais,André Ortlieb, AU - Levitsky,Victor, AU - Chen,Qijun, AU - Falk,Kerstin I, AU - Orem,Jackson, AU - Kironde,Fred, AU - Wahlgren,Mats, AU - Bejarano,Maria Teresa, PY - 2006/11/30/received PY - 2007/04/19/accepted PY - 2007/6/15/pubmed PY - 2007/10/6/medline PY - 2007/6/15/entrez SP - e80 EP - e80 JF - PLoS pathogens JO - PLoS Pathog VL - 3 IS - 6 N2 - Although malaria and Epstein-Barr (EBV) infection are recognized cofactors in the genesis of endemic Burkitt lymphoma (BL), their relative contribution is not understood. BL, the most common paediatric cancer in equatorial Africa, is a high-grade B cell lymphoma characterized by c-myc translocation. EBV is a ubiquitous B lymphotropic virus that persists in a latent state after primary infection, and in Africa, most children have sero-converted by 3 y of age. Malaria infection profoundly affects the B cell compartment, inducing polyclonal activation and hyper-gammaglobulinemia. We recently identified the cystein-rich inter-domain region 1alpha (CIDR1alpha) of the Plasmodium falciparum membrane protein 1 as a polyclonal B cell activator that preferentially activates the memory compartment, where EBV is known to persist. Here, we have addressed the mechanisms of interaction between CIDR1alpha and EBV in the context of B cells. We show that CIDR1alpha binds to the EBV-positive B cell line Akata and increases the number of cells switching to the viral lytic cycle as measured by green fluorescent protein (GFP) expression driven by a lytic promoter. The virus production in CIDR1alpha-exposed cultures was directly proportional to the number of GFP-positive Akata cells (lytic EBV) and to the increased expression of the EBV lytic promoter BZLF1. Furthermore, CIDR1alpha stimulated the production of EBV in peripheral blood mononuclear cells derived from healthy donors and children with BL. Our results suggest that P. falciparum antigens such as CIDR1alpha can directly induce EBV reactivation during malaria infection that may increase the risk of BL development for children living in malaria-endemic areas. To our knowledge, this is the first report to show that a microbial protein can drive a latently infected B cell into EBV replication. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/17559303/A_molecular_link_between_malaria_and_Epstein_Barr_virus_reactivation_ L2 - https://dx.plos.org/10.1371/journal.ppat.0030080 DB - PRIME DP - Unbound Medicine ER -