INDUCTION OF T-CELL APOPTOSIS BY HUMAN HERPESVIRUS-6

The mechanisms of cell death in CD4(+) T cells mediated by human herpe svirus 6 (HHV-6) were investigated. The frequency of cell death in the human CD4(+) T-cell line JJHAN, which had been inoculated with HHV-6 variant A or B, appeared to be augmented by tumor necrosis factor alph a (TNF-alpha). Agarose gel electrophoresis of DNA from HHV-6-inoculate d cells showed DNA fragmentation in multiples of the oligonucleosome l ength unit, The degree of DNA fragmentation increased when HHV-6-inocu lated cells were cultured in the presence of TNF-alpha. Flow cytometry and Scatchard analysis of TNF receptors revealed an increase in the n umber of the p55 form of TNF receptors on JJHAN cells after HHV-6 inoc ulation, It also appeared that treatment with anti-Fas monoclonal anti body (MAb) induced marked apoptosis in HHV-6-inoculated cells, Transmi ssion electron microscopy showed characteristics of apoptosis, such as chromatin condensation and fragmentation of nuclei, but virus particl es were hardly detected in apoptotic cells, Two-color flow cytometric analysis using anti-HHV-6 MAb and propidium iodide revealed that DNA f ragmentation was present predominantly in uninfected cells but not in productively HHV-6-infected cells, In addition, JJHAN cells incubated with UV light-irradiated and ultracentrifuged culture supernatant of H HV-6-infected cells appeared to undergo apoptosis, The present study d emonstrated that both HHV-6 variants A and B induce apoptosis in CD4() T cells by indirect mechanisms, as reported recently in human immuno deficiency virus type 1 infection.