New Type B Isolates of Epstein--Barr Virus from Burkitt's Lymphoma and from Normal Individuals in Endemic Areas

Abstract

SUMMARYAll Epstein-Barr virus (EBV) isolates can be classified as type A or type B depending upon the identity of their EBV nuclear antigen (EBNA) 2 protein. The great majority of isolates examined to date encode an EBNA 2A protein like that of the reference type A strain B95-8. Type B virus strains, encoding an antigenically distinct EBNA 2B protein, have as yet only been rescued from rare Burkitt's lymphoma (BL) cell lines of African origin (Jijoye, AG876). Our recent finding that type B isolates are less efficient than type A in in vitro transformation assays prompted us to determine (i) the relative contribution the two types of virus make to the incidence of BL in endemic areas of Africa (Kenya) and New Guinea and (ii) the relative incidence of infection with these two types in the normal population in these same areas. On the first point, EBNA 2 gene typing using specific DNA probes showed that four of ten recently established Kenyan BL cell lines and two of four BL cell lines from New Guinea carried type B virus isolates. To address the second point, spontaneous lymphoblastoid cell lines were established from the blood of normal virus carriers and typed for EBNA 2 at the protein level; a significant proportion (> 20 ~) of the normal population in both the above BLendemic areas were infected with type B isolates. This is the first indication of the widespread nature of type B virus infection in any community and the first isolation of such viruses from a non-BL source. The reproducible size of the EBNA 2B protein encoded by all type B isolates irrespective of their geographical origin, and of the EBNA 1 protein encoded by all type B isolates from one area, contrasted markedly with the extreme variability in the size both of EBNA 2A and of EBNA 1 seen generally among type A isolates. This suggests that the number of type B virus strains in existence worldwide could be quite limited. Most importantly, the data suggest that type B viruses, despite their relatively poor performance in in vitro transformation assays, can contribute at least as efficiently as can type A viruses to the pathogenesis of BL.

Prevalence of the A and B types of Epstein-Barr virus DNA in nasopharyngeal carcinoma biopsies from Southern China

“…The proportion of type A virus found in the present study of Chinese samples concurs with the overwhelming predominance of this type observed in several other geographical regions (Zimber et al, 1986;Yao et al, 1991). Only in areas of Africa and Papua New Guinea does the frequency of B type EBV appear to be significantly greater (Zimber et al, 1986;Young et al, 1987). The current viewpoint is that, at least in the case of Burkitt's lymphoma, the ratio of A type to B type virus in the tumour reflects the prevalence of infection within the general population.…”

Host cell phenotype-dependent methylation patterns of Epstein--Barr virus DNA

“…We have also found that CCGG sequences are highly methylated in the coding regions of EBNA I and LMP in Rael cells, but are unmethylated in an LCL that carried the same virus, rescued from Rael by cocultivation with cord blood cells . In C15, a nude mouse-passaged NPC cell line, the BamHI W fragment repeats and LMP coding sequences are highly methylated, whereas they Ernberg et al (1986); (3) Kallin et al (1986); (4) Young et al (1987); (5) this study, data not shown; (6) Ernberg et aL (1989).…”

Unusually high frequency of a 69-bp deletion within the carboxy terminus of the LMP-1 oncogene of Epstein–Barr virus detected in Burkitt’s lymphoma of Turkish children

“…10,12,17 Previous reports indicated that type A EBV is predominant in Western countries, in contrast to type B, which has been found mainly in central Africa and in New Guinea. 18,19 Cell lines containing type A virus had significantly higher growth rates and achieved much higher saturation densities than did type B strains. 20 EBV LMP-1 is a transforming oncogene in rodent fibroblasts Rat-1 21 and Balb/3T3 cells.…”