A new tumour-derived transforming strain of Epstein–Barr virus

Abstract

EPSTEIN–BARR VIRUS (EBV) has been associated with several diseases, including infectious mononucleosis (IM), Burkitt's lymphoma, and nasopharyngeal carcinoma. If EBV has an aetiological role in more than one of these diseases, explanations for pathogenic plurality must be sought. Host and environmental factors may influence the outcome of EBV infection, but recent descriptions of different EBV ‘strains’ have focused attention on the possibility that different virus strains may be associated with each of the above diseases^1–3. Although virus strains have not been differentiated by antigenic expression⁴, two major biological patterns have been delineated^5–7—strains capable of ‘transforming’ human cord blood lymphocytes to Epstein–Barr nuclear antigen (EBNA) positivity and ‘immortalised’ growth characteristics, and strains which lack this capability. In particular, the rare viral particles contained in throat washings from patients with active IM or Burkitt's lymphoma have such in vitro transforming capabilities^8–10. Until now, however, sufficient virus for biochemical study has been obtained from only two continuous lymphoblastoid cell lines. Fortuitously, the viruses from these two lines have different biological properties. The B95-8 cell line produces a virus with transforming characteristics which was originally derived from the peripheral blood of a patient with transfusion-induced IM, and was passaged and maintained in lymphocytes of the cotton-topped marmoset¹¹. It is possible, however, that deletion or addition of nucleotide sequences has occurred as a result of the continued propagation of this virus in the cells of a subhuman primate. A second virus strain is produced by the P3HR1 cell line. This cell line was originally derived from the JlJoye Burkitt's lymphoma cell line by soft agar cloning¹². The virus produced by this cell line is generally incapable of in vitro ‘transformation’^5,6, but will induce early antigen (EA) in the EBV genome-positive non-producing RAJI cell line¹³. EBV produced during early passage(s) of the original P3HR1 cell line had in vitro ‘transforming’ capability¹⁴, but subseqeuntly lost this property. Studies by Zur Hausen¹⁵ have suggested that a P3HR1 cell line produces a mixture of EBNA transforming and EA-inducing virus. This raises the possibility of a mutation in the P3HR1 virus and concern regarding its use as a prototype or ‘reference’ strain of EBV. We report here the isolation of a new tumour-derived strain of EBV which has been propagated only in its cell of origin, and which manifests in vitro ‘transforming’ capability, making it a more representative ‘wild-type’ or putative tumour virus strain of EBV.