PMID- 9094650 OWN - NLM STAT- MEDLINE DCOM- 19970425 LR - 20200724 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 71 IP - 5 DP - 1997 May TI - Induction of T-cell apoptosis by human herpesvirus 6. PG - 3751-9 AB - The mechanisms of cell death in CD4+ T cells mediated by human herpesvirus 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 alpha (TNF-alpha). Agarose gel electrophoresis of DNA from HHV-6-inoculated cells showed DNA fragmentation in multiples of the oligonucleosome length unit. The degree of DNA fragmentation increased when HHV-6-inoculated cells were cultured in the presence of TNF-alpha. Flow cytometry and Scatchard analysis of TNF receptors revealed an increase in the number of the p55 form of TNF receptors on JJHAN cells after HHV-6 inoculation. It also appeared that treatment with anti-Fas monoclonal antibody (MAb) induced marked apoptosis in HHV-6-inoculated cells. Transmission electron microscopy showed characteristics of apoptosis, such as chromatin condensation and fragmentation of nuclei, but virus particles were hardly detected in apoptotic cells. Two-color flow cytometric analysis using anti-HHV-6 MAb and propidium iodide revealed that DNA fragmentation 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 HHV-6-infected cells appeared to undergo apoptosis. The present study demonstrated that both HHV-6 variants A and B induce apoptosis in CD4+ T cells by indirect mechanisms, as reported recently in human immunodeficiency virus type 1 infection. FAU - Inoue, Y AU - Inoue Y AD - First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan. FAU - Yasukawa, M AU - Yasukawa M FAU - Fujita, S AU - Fujita S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (fas Receptor) SB - IM MH - *Apoptosis MH - CD4-Positive T-Lymphocytes/pathology/*virology MH - Cells, Cultured MH - DNA Fragmentation MH - Flow Cytometry MH - Herpesvirus 6, Human/*physiology MH - Humans MH - Proto-Oncogene Proteins c-bcl-2/analysis MH - Receptors, Tumor Necrosis Factor/analysis MH - Tumor Necrosis Factor-alpha/pharmacology MH - fas Receptor/physiology PMC - PMC191525 EDAT- 1997/05/01 00:00 MHDA- 1997/05/01 00:01 PMCR- 1997/05/01 CRDT- 1997/05/01 00:00 PHST- 1997/05/01 00:00 [pubmed] PHST- 1997/05/01 00:01 [medline] PHST- 1997/05/01 00:00 [entrez] PHST- 1997/05/01 00:00 [pmc-release] AID - 10.1128/JVI.71.5.3751-3759.1997 [doi] PST - ppublish SO - J Virol. 1997 May;71(5):3751-9. doi: 10.1128/JVI.71.5.3751-3759.1997.