Asymptomatic Epstein-Barr virus (EBV) reactivations periodically occur in oral mucosa-associated lymphoid tissues. Until now, EBV reactivation has been diagnosed by serologic profiles that suggest virus replication. Serologic responses, however, are delayed and do not necessarily indicate ongoing replicative activity. The aim of the present study was to establish in healthy carriers parameters for a molecular diagnosis of reactivated EBV infection. Recent studies emphasized the association of an increase in peripheral-B-cell viral load with replicative activity at remote sites. Therefore, real-time PCR was used to quantitate EBV genomes in the peripheral blood mononuclear cells (PBMC) (viral load) and plasma samples (viremia) of 22 healthy EBV-seropositive blood donors over a period of 15 months. Furthermore, transcription of the immediate-early gene encoding BZLF1 was investigated in the PBMC of all volunteers. Serology suggested reactivation in nine donors, of whom all but one showed at least once a significant increase in viral load. Another five individuals also exhibited significant changes in viral load but no serologic response. Of the 13 volunteers with significant increases in viral load, 6 had a period of viremia accompanying the rise in viral load. A stable viral load without viremia and negative serology was seen in eight adults. BZLF1 mRNA was undetectable throughout. We conclude that for healthy subjects serology underestimates the frequency of asymptomatic EBV reactivations. Prospective examination of peripheral viral load and viremia is suitable for the exact diagnosis of EBV reactivation, which might be of advantage for immunocompromised patients in whom EBV reactivations are considerably harmful.

The onset and frequency of Epstein-Barr virus (EBV) reactivation after kidney transplantation are unknown. By use of quantitative real-time polymerase chain reaction measurements, evidence of early EBV reactivation, occurring within the first week after the initiation of immunosuppressive therapy (median, 3 days), was observed in 13 of 23 patients, of whom 10 subsequently developed rejection episodes after 2-45 days (median, 5 days). By contrast, rejection was only diagnosed in 1 of 10 patients who did not show signs of viral reactivation. We suggest that EBV reactivation may induce a T cell response that, through the phenomenon of allo-cross-reactivity, could play a critical role in graft rejection.

IntroductionChemokines are important mediators of the immune system with primarily chemotactic properties. By recruiting phagocytes as well as lymphocytes to extranodal sites of inflammation, chemokines connect unspecific with specific compartments of the immune system and therefore play a pivotal role in developing a rapid, focused, and effective immune response (for a review, see Rollins 1 ).Chemokines are classified as C, CC, CXC, or CX 3 C chemokines on the basis of the arrangement of 1 or 2 N-terminal cysteine residues. 2 CXC and CC chemokines consist of multiple 8-to 10-kd proteins each with overlapping, but to some extent, opposite actions. 3 CXC chemokines, such as interleukin-8 (IL-8), almost exclusively act on neutrophils, whereas chemokines of the CC group, such as RANTES (regulated on activation normal T cell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), or macrophage inflammatory protein-1␣ (MIP-1␣) have a broader spectrum of action predominantly attracting monocytes, macrophages, lymphocytes, and natural killer (NK) cells. 3 CC chemokines, especially MIP-1␣, proved to be key elements in the development of antiviral immunity. 4 Besides promotion of coxsackievirus B3-induced myocarditis, MIP-1␣ is indispensable for viral clearance in influenza virus-induced pneumonitis in vivo. 5 Moreover, MIP-1␣ is critical for protection against murine cytomegalovirus infection in vivo through recruitment of NK cells and accompanied interferon gamma (IFN-␥) production. 6 Together with MIP-1␤ and RANTES, MIP-1␣ was identified as one of the major human immunodeficiency virus (HIV)-suppressive factors secreted by CD8 ϩ T cells. 7 Further actions of MIP-1␣ comprise the modulation of macrophage functions, such as stimulation of tumor necrosis factor ␣ (TNF-␣) production, 8 the preferential chemotaxis of CD8 ϩ T cells 4 as well as the inhibition of hematopoietic stem cell proliferation. 1 Another indication of its important role in antiviral defense derives from Kaposi sarcoma-associated herpesvirus (KSHV). KSHV integrated into its genome homologues of human MIP-1␣ that are assumed to counteract some functions of the human homologue. 9,10 An MIP-1␣ homologue encoded by other human herpesviruses, including Epstein-Barr virus (EBV), has not been described yet. However, the rhesus macaque rhadinovirus, which seems to be the homologue to KSHV, as well as human molluscum contagiosum poxvirus also encode for viral CC chemokines, the latter one acting as an antagonist on human chemokine receptor CCR8. 11,12 Epstein-Barr virus is a human herpesvirus with a selective tropism for B lymphocytes and is associated with certain human malignancies. 13 Lifelong EBV infection is established in the long-living compartment of resting memory B cells. 14 Reactivation is presumably achieved by infected B cells, which intermittently recirculate to secondary lymphoid tissues. 14 The cellular and subcellular events of EBV reactivation are only poorly understood. Little is known about the influence of EBV on the chemokine syst...

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