Heterogeneous, restricted patterns of Epstein-Barr virus (EBV) latent geneexpression in patients with chronic active EBV infection

Epstein-Barr virus (EBV) has been shown to infect T lymphocytes and to be a ssociated with a chronic active infection (CAEBV), which has been recognize d as a mainly non-neoplastic T-cell lymphoproliferative disorder (T-cell LP D). The systemic distribution of EBV genomes was studied, by real-time PCR, in multiple tissues from six patients with CAEBV, including three patients with T-cell LPD, one patient with B-cell LPD and two patients with undeter mined cell-type LPD. There were extremely high loads of EBV genomes in all tissues from the patients. This reflects an abundance of circulating and in filtrating EBV-infected cells and a wide variety of clinical symptoms in th e affected tissues. We chose one sample from each patient that was shown by real-time PCR to contain a high load of EBV genomes and examined the expre ssion of EBV latent genes by RT-PCR. EBER1 and EBNA1 transcripts were detec ted in all samples. Only one sample also expressed EBNA2, LMP1 and LMP2A tr anscripts in addition to EBER1 and EBNA1 transcripts. Two of the remaining five samples expressed LMP1 and LMP2A transcripts. One sample expressed LMP 2A but not LMP1 and EBNA2 transcripts. Another sample expressed EBNA2 but n ot LMP1 and LMP2A transcripts. The other sample did not express transcripts of any of the other EBNAs or LMPs. None of the samples expressed the viral immediate-early gene BZLF1. These results showed that EBV latent gene expr ession in CAEBV is heterogeneous and that restricted forms of EBV latency m ight play a pathogenic role in the development of CAEBV.