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English: Fig. 1. Pathogenetic mechanisms of early onset EBV-related PTLD. PAMPs and DAMPs, through TLRs, promote the release of pro-inflammatory cytokines, which in turn activate EBV lytic cycle. At early stage of disease, lytic replication of EBV leads to increased number of infected cells. Moreover, B-cell activation, due to persistent inflammation/immune activation, may also favor expansion of EBV-infected B cells, leading to a significant increase in EBV load in peripheral blood mononuclear cells, a crucial step for PTLD development. Along with infection, the oncogenic LMP-1 viral protein transcriptionally activates TERT, the catalytic component of telomerase activity, which in turn blocks lytic viral replication. EBV-infected B cells expressing LMP-1 and cellular TERT protein are prone to transformation. Levels of circulating products involved in inflammation/activation, as well as increased EBV-DNA levels, may predict PTLD onset. Circulating TERT, released from TERT-positive cells, may be useful in monitoring disease outcome.