IN-VITRO CYTOBIOLOGICAL EFFECTS OF HUMAN-HERPESVIRUS-6 AND HUMAN-HERPESVIRUS-7 - IMMUNOHISTOLOGICAL MONITORING OF APOPTOSIS, DIFFERENTIATION AND CELL-PROLIFERATION

Two human herpesviruses, HHV-6 and HHV-7, recently identified and clos ely related were studied for their influence on cellular apoptosis and proliferation. Infection was monitored by viral DNA-and antigen expre ssion. Apoptosis and cell proliferation were determined by immunocytol ogical techniques and the markets p53, p21WAF/Cip, Bax, Bak, Bcl-2, cy clin D1 and PCNA, and also screened for signal transduction indicators such as c-H-ras, c-fos and raf-1. Cell differentiation and function w as monitored by determining cell membrane receptors including Fas and CD specificities, and by ELISA tests for interleukin production. Both HHV-6 and HHV-7 readily infected their target cells, yet vine antigen expression and virus replication were less active in HHV-7 infection. Both viruses also induced GM-CFS production. Cell differentiation in t erms of CD receptor expression was more pronounced in HHV-6 than in HH V-7 infection. No differences were found in the activity of signal tra nsduction factors. There were quantitative differences in the activati on of p53, Bax, p21WAF and Bcl-2 in HHV 6-infected CBC as compared to HHV-7 infection supporting the apoptosis cycle. CyclinD1 activity rema ined at lower levels in HHV-7 infected CBC, yet was high in similarly infected transformed SupT1 cells. In contrast, HHV-6 supported rather the p53/p21WAF apoptosis pathway in both untransformed CBC and transfo rmed HSB1 cells. Both herpesviruses, HHV-6 and HHV-7, thus possessed s imilar biological activities in cultures of non-transformed susceptibl e cells, although with certain quantitative differences. The data repo rted here may further support the notion that HHV-7 is less active in inducing apoptosis thus favoring continued cell proliferation. The mec hanism by which these viruses interfere with the network control of ce ll proliferation, differentiation and apoptosis appear more complicate d than shown here and therefore afford a more detailed study, includin g a more sensitive technology than immunohistology.