Distinction between Epstein-Barr virus type A (EBNA 2A) and type B (EBNA 2B) isolates extends to the EBNA 3 family of nuclear proteins

Abstract

The Epstein-Barr virus (EBV) nuclear antigens EBNA 3a, 3b, and 3c have recently been mapped to adjacent reading frames in the BamHI L and E fragments of the B95.8 EBV genome. We studied by immunoblotting the expression of the family of EBNA 3 proteins in a panel of 20 EBV-transformed lymphoblastoid cell lines (LCLs) carrying either type A (EBNA 2A-encoding) or type B (EBNA 2B-encoding) virus isolates. Certain human sera from donors naturally infected with type A isolates detected the EBNA 3a, 3b, and 3c proteins in all type A virus-transformed LCLs (with a single exception in which EBNA 3b was not detected) but detected only EBNA 3a in LCLs carrying type B isolates. These results were confirmed with human and murine antibodies with specific reactivity against sequences of the type A EBNA 3a, 3b, or 3c expressed in bacterial fusion proteins. Conversely, selected human sera from donors naturally infected with type B strains of EBV identified the EBNA 3a encoded by both types of isolates plus two novel EBNAs present only in type B, and not in type A, virus-transformed LCLs; these novel proteins appear to be the type B homologs of EBNA 3b and 3c. The distinction between type A and type B EBV isolates therefore extends beyond the EBNA 2 gene to the EBNA 3 family of proteins. This has important implications with respect to the evolutionary origin of these two EBV types and also places in a new light recent studies which identified differences between type A and type B transformants in terms of growth phenotype (A. B.

Detection of multiple Epstein‐Barr viral strains in allogeneic bone marrow transplant recipients

“…Similar variants have not been detected among the blood lymphocyte-derived EBV strains that we have studied. These findings also suggest that recombination during lytic viral DNA replication in the oropharyngeal epithelium may serve as the basis for the polymorphism of EBV in unrelated individuals [Ernberg et al, 1986;Gratama et al, 1988Gratama et al, , 1990aGratama et al, , 1990bRowe et al, 1989;Sculley et al, 1987, 19901. However, the identical Ebnotypes of EBV strains carried by several family members [Gratama et al, 1990bl suggests that numerous horizontal transmission steps may have to take place before genetic differences between EBV strains carried by blood lymphocytes become apparent.…”

“…The combined size variations of Epstein-Barr virus (EBV) nuclear antigens EBNA 1,2,3,4, and 6 in irnrnunoblots of lymphoblastoid cell lines (LCL) have been used to distinguish between different EBV strains [Ernberg et al, 1986;Gratama et al, 1988Gratama et al, , 1990aGratama et al, , 1990bRowe et al, 1989;Sculley et al, 1987,19901. We have used this "Ebnotyping" approach to distinguish between donor and recipient virus in bone-marrowgrafted patients [Gratama et al, 1988.…”

DNA of lymphoma‐associated herpesvirus (HVMF1) in SIV‐infected monkeys (Macaca fascicularis) shows homologies to EBNA‐1, ‐2 and ‐5 genes

“…As mentioned, EBV can be sub-grouped into type-A and type-B viruses, which are distinguished on the basis of the EBNA2 sequence, but also differ in EBNA3,4 and 6 sequences (Rowe et al, 1989;Sample et al, 1990). In HVMF1, the CYNA2 sequence is more homologous to that of type-A EBV.…”

Epstein‐Barr virus: Biology and disease

“…The strains appear to be identical over the bulk of the EBV genome but show polymorphism (with 50-80% sequence homology depending on the locus) Figure 1 EBV. epithelial cells and lymphocytes: their possible role and interaction in viral infection and persistence SIS7 in a subset of latent genes, namely those encoding EBNA-LP, EBNA2, EBNA3A, EBNA3B and EBNA3C (Darnbaugh et al, 1984;Rowe et al, 1989;Sample et al, 1990). A combination of virus isolation and sero-epiderniological studies suggest that type I virus isolates are predominant (but not exclusively so) in many western countries, whereas both types are widespread in equatorial Africa, New Guinea and perhaps certain other regions (Zirnber et al, 1986;Young et al, 1987;Sixbey et al, 1989;Yao et al, 1991).…”