EPSTEIN-BARR-VIRUS (EBV) INFECTION IN INFECTIOUS-MONONUCLEOSIS - VIRUS LATENCY, REPLICATION AND PHENOTYPE OF EBV-INFECTED CELLS

Primary Epstein-Barr virus (EBV) infection may manifest itself as a be nign lymphoproliferative disorder, infectious mononucleosis (IM). EBV infection has been characterized in lymphoreticular tissues from nine patients,vith IM using the abundantly expressed EBV-encoded nuclear RN As (EBERs) as a marker of latent infection. Expression of the virus-en coded nuclear antigen (EBNA) 2 and of the latent membrane protein (LMP ) 1 was seen in variable proportions of cells in all cases. Double lab elling revealed heterogeneous expression patterns of these proteins. T hus, in addition to cells revealing phenotypes consistent with latenci es I (EBNA2(-)/ILMP1(-)) and III (EBNA(2+)/LMP1(+)), cells displaying a latency II pattern (EBNA2(-)/LMP1(+)) were observed. Cells expressin g EBNA2 but not LMP1 were also detected; whilst this may represent a t ransitory phenomenon, the exact significance of this observation is at present uncertain. EBER-specific in situ hybridization in conjunction with immunohistochemistry revealed expression of the EBERs mainly in B-lymphocytes, many of which showed features of plasma cell differenti ation. By contrast, convincing evidence of latent EBV infection was no t found in T-cells, epithelial or endothelial cells. Double-labelling immunohistochemistry revealed expression of the replication-associated BZLF1 protein in small lymphoid cells, often showing plasmacytoid dif ferentiation. There was no unambiguous expression of this protein in o ther cell types. These results suggest that B-cells are the primary ta rget of EBV infection and that plasma cells may be a source of infecti ous virus found in the saliva of IM patients. (C) 1997 by John Wiley & Sons, Ltd.