A Molecular Link between Malaria and Epstein–Barr Virus Reactivation

PLoS Pathogens

Arnaud Chêne¹  Victor Levitsky¹  Daria Donati²  Kerstin I Falk²  Qijun Chen²  Fred Kironde²  Jackson Orem³  André Ortlieb Guerreiro-Cacais³  Mats Wahlgren³  Maria Teresa Bejarano⁴ 

[1] Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden;Swedish Institute for Infectious Disease Control, Stockholm, Sweden;Uganda Cancer Institute, Kampala, Uganda

关键词: B cells;    Viral replication;    Malaria;    Epstein-Barr virus;    Glutathione chromatography;    Tonsils;    Viral persistence;    latency;    Lytic cycle;   

DOI  :  10.1371/journal.ppat.0030080

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 1α (CIDR1α) 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 CIDR1α and EBV in the context of B cells. We show that CIDR1α 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 CIDR1α-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, CIDR1α 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 CIDR1α 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.

【 授权许可】

CC BY