Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection.

Abstract

Five distinct Epstein-Barr virus (EBV)-deterinned nuclear antigens (EBNA-1 to were recently identified. Antibody responses to these antigens could conceivably differ, and thus prove of serodiagnostic value, in EBVassociated disease processes. As a rst step, murine or human cell lines transfected with appropriate EBV DNA fragments and stably expressing either EBNA-1 or EBNA-2 were used to determine the frequency and time of emergence of antibodies to these two antigens in the course of acute and chronic infectious mononucleosis (IM) and to assess their titers in so-called chronic active EBV infections. Following IM, pntibodies to EBNA-2 arose first and, after reaching peak titers, declined again in time to lower persistent or even nondetectable levels. Antibodies to EBNA-1 emerged several weeks or months after anti-EBNA-2 and gradually attained the titers at which they persisted indefinitely. The ratios between the anti-EBNA-1 and anti-EBNA-2 titers therefore were generally well below 1.0 during the first 6-12 months after IM and turned to well above 1.0 during the second year. In clear cases of chronic IM, the inversion of this ratio was delayed or prevented. In the less well-defined chronic EBV infections, low ratios were observed in only some of the patients. Because many of these illnesses were not ushered in by a proven IM and often showed EBV-specific antibody profiles within the normally expected range, a causal role of the virus in these cases remains doubtful.

The Importance of Exogenous Antigen in Priming the Human CD8+ T Cell Response: Lessons from the EBV Nuclear Antigen EBNA1

“…However, we speculated that the induction of the EBNA1 response might be delayed because this requires prior Ag release and, arguably, such release may depend upon an effective CTL response to latently infected cells having already been mounted. This would provide an interesting parallel to the humoral response to primary infection, in which Abs to EBNA1, but not to the other EBNAs, develop unusually late (36,37). In fact, we consistently observed that the primary CTL response to the B*3501-restricted EBNA1/HPV epitope was at least as strong as that seen in the same individuals to the EBNA3A/YPL epitope and comparable to other immundominant latent epitopes.…”

Characterization of the Serological Response in Man to the Latent Membrane Protein and the Six Nuclear Antigens Encoded by Epstein-Barr Virus

“…Henle et al (1987), using an immunofluorescence test similar to that of Dillner et al (1987) and Seigneurin et al (1987), demonstrated the presence of anti-EBNA 2 antibodies in 71 ~ of healthy EBV-immune controls, but neither NPC nor BL sera were included in their study. The different results obtained with NPC and BL sera with the two types of assay are not due simply to differences in sensitivity, since the immunoblotting assays actually detected a decreased anti-EBNA 2 response in NPC sera, which is in contrast to the increased incidence of antibodies reported using immunofluorescence tests.…”

Serological diagnosis of Epstein-Barr virus infection: Problems and solutions

“…However, some immunoblotting studies have found that 2% of subjects who have De Paschale M et al . Epstein-Barr virus serological diagnosis experienced previous infections may be negative for VCA IgG (anti-p23 or anti-p18) [23] and, although rare, this pattern can be found in routine laboratory tests and may represent about 1.7% of all EBNA-1 IgG-positive samples [39] . An isolated EBNA-1 IgG pattern therefore gives rise to some interpretative doubts: it is possible to envisage aspecific EBNA-1 IgG, a lack of VCA IgG production or their loss over time.…”

“…Children and adults with primary infection are not always positive for VCA IgM [32,38] . Anti-EBNA-2 IgG (EBNA-2 IgG) appear early, and may be present in up to 30% of the patients in the course of disease [2,23] , whereas anti-EBNA-1 IgG (EBNA-1 IgG) is usually undetectable during the first 3-4 wk after the onset of clinical symptoms [32,39] and is therefore indicative of past infection. Furthermore, most patients with chronic infection and immunosuppressed patients are negative for EBNA-1 IgG or have only low levels [40] .…”