APOPTOSIS AND CELL-PROLIFERATION IN HHV-6 INFECTION - REGULATION BY P53 BCL-2/RAS INTERACTIONS/

HHV-6 infected immature T (HSB 2) and Hodgkin (HDLM 2) cells and biops y tissues from lymph nodes of patients with Hodgkin's disease (HD) and Kikuchi lymphadenitis (KL) were studied immunohistologically for viru s antigen expression and for the oncogene/anti-oncogene products ras, bcl-2 and p53. Cell proliferation and cell death were tentatively moni tored in tissue culture by PCNA staining, by viability testing and in situ end labeling of fragmented DNA. PCNA was also used in biopsy samp les. KL is characterized by high incidences of focal cell death (i.e. histiocytic necrotizing lymphadenitis), while HD is apparently more a proliferative disease. The techniques used revealed no significant dif ferences in the cellular expression of viral DNA or antigens among cel l lines, HD or KL. The HDLM 2 cell line with the superior survival aft er HHV-6 infection showed a significantly lower expression of p53 and PCNA than HSB 2 cells. Biopsy samples from patients with KL did not ex press p53, and ras and PCNA were observed in fewer cells than in HD. B cl-2, however, was significantly more frequently seen than in HD. The interpretation of the data is difficult; they suggest that there are a dditional regulatory influences in control of cell proliferation and c ell death, such as cytokines and growth factors, which are altered aft er viral infection. Also, virus-induced cell death probably includes o ther mechanisms besides apoptosis, such as cell damage caused by oxyge n radicals.