ENFORCED EXPRESSION OF HUMAN BCL-2 IN CD4(-CELLS ENHANCES HUMAN-HERPESVIRUS-7 REPLICATION AND INDUCTION OF CYTOPATHIC EFFECTS() T)

The cytopathic effects (CPE) resulting from the infection of CD4(+) T cells by human herpesvirus 7 (HHV-7) comprises two major mechanisms: g eneration of large polyploid cells, which eventually undergo necrotic lysis, and apoptosis, predominantly occurring in small mononucleated c ells. To dissect the relative contribution of these two phenomena to t he overall cytopathicity of HHV-7 in vitro, we have investigated the e ffect of acute HHV-7 infection on SupT1 CD4(+) T cell lines stably tra nsfected either with the bcl-2 anti-apoptotic gene or with the control vector. Overexpression of Bcl-2 protein by these cells was associated with a progressive decline of the total number of viable cells, and a relative increase of enlarged polyploid cell. Of note, the size of po lyploid cells was significantly greater in SupT1 cells overexpressing bcl-2 than in cells transfected with the control vector. In addition, bcl-2 expression accelerated the kinetics of an acute spreading of HHV -7 infection, as determined by HHV-7-specific indirect immunostaining revealed by either fluorescence microscopy or flow cytometry. Our resu lts indicate that inhibition of apoptosis in HHV-7-infected cultures g reatly favors the process of polyploidization and represents a major m echanism to maximize viral transmission.