Phenotype and frequency of Epstein-Barr virus-infected cells in pretreatment blood samples from patients with Hodgkin lymphoma.

An accumulating body of data suggests that the Epstein-Barr virus (EBV), a lymphotropic herpesvirus, is involved in the pathogenesis of a proportion of cases of Hodgkin lymphoma (HL). In this study, we showed that the frequency of circulating EBV-infected cells was significantly higher (P < 0.001) in pretreatment blood samples from EBV-associated cases when compared with non-EBV-associated cases. We further showed that in patients with EBV-associated disease, the virus persisted in the peripheral blood in memory B cells. This phenotype is consistent with that seen in healthy seropositive controls, post-transplant patients and patients with acute infectious mononucleosis. The data suggest that an increased frequency of EBV carrying B cells in peripheral blood is associated with EBV-associated HL.

Management of cytomegalovirus infection by weekly surveillance after renal transplant: analysis of cost, rejection and renal function.

BACKGROUND: Recently published guidelines recommend anti-viral prophylaxis as the best method of preventing cytomegalovirus (CMV) disease in the post-transplant period, but some authors have suggested that surveillance strategies may be as effective and less costly. The aim of the present study was to analyse the effectiveness and cost of a deferred treatment strategy using weekly CMV polymerase chain reaction (PCR) surveillance in high risk renal transplant recipients. METHODS: We used weekly surveillance for plasma CMV PCR positivity for the first 3 months in consecutive renal transplants between CMV seropositive donors and seronegative recipients, and analysed incidence of CMV infection, timing of infection, acute rejection and renal function at 1 year. RESULTS: There was evidence of CMV infection in 27/41 (65.9%) patients and of CMV disease in 20/41 (48.8%). Only 8/20 (40%) patients were PCR positive before disease onset. Patients were treated on the basis of clinical evidence of CMV disease (deferred strategy), but we used the data to compare the potential costs of a pre-emptive strategy (all patients PCR positive before the onset of clinical features of disease treated with intravenous ganciclovir) and prophylaxis (oral ganciclovir for 3 months in all patients). The deferred strategy cost pound 1159 per patient (excluding the cost of hospitalization) while a pre-emptive strategy would cost pound 1381 per patient. Prophylaxis costs pound 1500- pound 2213 per patient depending on published estimates of relative risk reduction. Mean estimated creatinine clearance at 1 year was 70.0 ml/min in patients who experienced no infection, 47.7 ml/min in patients who experienced infection but no disease, and 39.6 ml/min in patients who experienced CMV disease (P < 0.001). The incidence of acute rejection in these groups was 7.1, 14.3 and 35%, respectively (P = 0.13). CONCLUSIONS: CMV surveillance strategies may cost slightly less but may have a deleterious effect on long-term outcome compared with prophylaxis.

Characterisation of the differences between hepatitis C virus genotype 3 and 1 glycoproteins.

Sequence variation in the envelope E1 and E2 glycoproteins of hepatitis C virus (HCV) could account for differences in disease pathogenesis in patients infected with different genotypes. A cDNA encoding the structural region of the hepatitis C polyprotein was constructed to match the majority sequence of viral RNA extracted from a patient infected with genotype 3a (designated strain HCV3a-Gla). The principal differences predicted between E2 of HCV3a-Gla and the corresponding H77c genotype 1a protein were that the former contained six more amino acids (361 vs. 355), but it had one fewer glycosylation site. Expression studies showed that, in common with the H77c glycoproteins, E1 and E2 from HCV3a-Gla localised to the endoplasmic reticulum (ER) membrane in both Huh-7 and BHK tissue culture cells and interacted to form native complexes. Analysis of the cross-reactivity of antibodies raised against glycoproteins of genotype 1a strains showed that three of five monoclonal antibodies that recognise linear epitopes were able to detect E2 from strain HCV3a-Gla. However, neither conformational E2 antibodies nor antibodies raised against E1 were able to detect the HCV3a-Gla glycoproteins. In receptor binding assays, E2 of HCV3a-Gla consistently failed to bind CD81, a putative cell receptor for HCV. Absence of binding to CD81 and lack of recognition by most antibodies raised to genotype 1a glycoproteins indicate important differences between these glycoproteins representative of genotypes 3a and 1a. These may be pertinent to the differences in response to interferon therapy and the prevalence of steatosis reported in patients infected with these genotypes.