HUMAN-HERPESVIRUS-7 INDUCES CD4(-CELL DEATH BY 2 DISTINCT MECHANISMS - NECROTIC LYSIS IN PRODUCTIVELY INFECTED-CELLS AND APOPTOSIS IN UNINFECTED OR NONPRODUCTIVELY INFECTED-CELLS() T)

We have investigated the cytopathic effects induced by the T-lymphotro pic human herpesvirus 7 (HHV-7) on the CD4(+) T-lymphoblastoid SupT1 c ell line and primary CD4(+) T lymphocytes. Acute in vitro HHV-7 infect ion induced (1) the formation of giant multinucleated syncytia, which eventually underwent necrotic lysis, and (2) single-cell apoptosis. Bo th cytopathic effects increased with the progression of infection and were blocked by phosphonoformic acid, a specific inhibitor of herpetic DNA polymerase. Using electron microscopy analysis of various samples , we found that all syncytia contained large amounts of virions and th at most of them exhibited clear evidence of necrosis, whereas apoptosi s was predominantly observed in single cells. Although empty viral cap sids could be identified in the cytoplasm of approximately 25% of sing le cells exhibiting an apoptotic morphology, mature virions were hardl y observed in these cells. In both coculture and cell-free HHV-7 infec tion experiments, a significant correlation was observed between the d egree of single-cell apoptosis, evaluated by quantitative flow cytomet ry after propidium iodide staining, and the decrease in the total numb er of viable cells. Moreover, in cell-free infection experiments, apop tosis showed a positive correlation also with the viral load, monitore d by quantitative HHV-7 DNA polymerase chain reaction, Thus, it appear s that apoptosis occurred predominantly in uninfected bystander cells hut not in productively HHV-7-infected cells. (C) 1997 by The American Society of Hematology.