Open AccessImmune activation suppresses initiation of lytic Epstein‐Barr virus infection
Author(s) -
Ladell Kristin,
Dorner Marcus,
Zauner Ludwig,
Berger Christoph,
Zucol Franziska,
Bernasconi Michele,
Niggli Felix K.,
Speck Roberto F.,
Nadal David
Publication year - 2007
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.00937.x
Subject(s) - lytic cycle , immune system , mononucleosis , immunology , biology , epstein–barr virus , virology , virus , peripheral blood mononuclear cell , innate immune system , immunity , in vitro , biochemistry
Summary Primary infection with Epstein‐Barr virus (EBV) is asymptomatic in children with immature immune systems but may manifest as infectious mononucleosis, a vigorous immune activation, in adolescents or adults with mature immune systems. Infectious mononucleosis and chronic immune activation are linked to increased risk for EBV‐associated lymphoma. Here we show that EBV initiates progressive lytic infection by expression of BZLF‐1 and the late lytic genes gp85 and gp350/220 in cord blood mononuclear cells (CBMC) but not in peripheral blood mononuclear cells (PBMC) from EBV‐naive adults after EBV infection ex vivo . Lower levels of proinflammatory cytokines in CBMC, used to model a state of minimal immune activation and immature immunity, than in PBMC were associated with lytic EBV infection. Triggering the innate immunity specifically via Toll‐like receptor‐9 of B cells substantially suppressed BZLF‐1 mRNA expression in acute EBV infection ex vivo and in anti‐IgG‐stimulated chronically latently EBV‐infected Akata Burkitt lymphoma cells. This was mediated in part by IL‐12 and IFN‐γ. These results identify immune activation as critical factor for the suppression of initiation of lytic EBV infection. We hypothesize that immune activation contributes to EBV‐associated lymphomagenesis by suppressing lytic EBV and in turn promotes latent EBV with transformation potential.