Viral and cellular modulation of virus-induced apoptosis in experimental infection models

The aim of this study was to investigate herpes simplex virus type 1 (HSV-1)- and measles virus (MV)-induced cell death. HSV-1 with deletion in genes encoding infected cell protein (ICP)4 and protein kinase Us3 (d120) induced apoptosis and cathepsin activation in epithelial (HEp-2) and monocytic (U937) cells. Inhibition of cathepsin activity decreased the amount of d120-induced apoptosis indicating that d120-induced apoptosis could be cathepsin-mediated. Also, HSV-1 infection increased caspase activation suggesting that d120-induced apoptosis is probably caspase-mediated. Cystatin treatment decreased the activity of cathepsins and the replication of HSV-1 indicating that cathepsins contribute to HSV-1 infection. Interestingly, d120 induced also necroptosis in monocytic cells. This is the first report on necroptosis in HSV-1- infected cells. MV induced apoptosis in uninfected bystander T lymphocytes, probably via interaction of MV-infected monocytes with uninfected lymphocytes. The expression of death receptor Fas was clearly increased on the surface of lymphocytes. The number of apoptotic cells and the activation of cathepsins and caspases were increased in MVinfected U937 cells suggesting that MV-induced apoptosis could be cathepsin- and caspase-mediated. Cystatin treatment inhibited cathepsin activities but not MV-induced apoptosis. Besides HSV-1-induced apoptosis, innate immune responses were studied in HSV-1-infection. HSV-1 viruses with either ICP4 and Us3, or Us3 deletion only, increased the expression of Toll-like receptor (TLR)3 and stimulated its downstream pathways leading to increased expression of type I interferon gene and to functional interferons. These findings suggest that besides controlling apoptosis, HSV-1 ICP4 and Us3 genes are involved in the control of TLR3 response in infected cell.

Effectiveness of the KiVa Antibullying Program

According to the participant role approach (Salmivalli, Lagerspetz, Björkqvist, Österman, & Kaukiainen, 1996), bullying is a group phenomenon that is largely enabled and maintained by the classmates taking on different participant roles (e.g., reinforcers or assistants of the bully). There is, however, very little evidence on whether the bystander behaviors actually have an effect on the risk for victimization. Furthermore, the participant role approach implies that the bystanders should be used in putting an end to bullying. This view has been put into practice in the KiVa antibullying program, but it has not yet been investigated whether the program is effective. Four studies were conducted to investigate, (a) whether the behaviors of bystanders have an effect on the risk for victimization (Study I) and (b) whether the KiVa program reduces bullying and victimization and has other beneficial effects as well (Studies II–IV). The participants included large samples of elementary and lower secondary school students (Grades 1–9) from Finland. The assessments were done with web-based questionnaires including questions about bullying and victimization (both self- and peer reports), and about several bullying-related constructs. The results of this thesis suggest that bystander behaviors in bullying situations may influence the risk for victimization of vulnerable students. Moreover, the results indicate that the KiVa antibullying program is effective in reducing victimization and bullying. The program effects are larger in elementary schools than in lower secondary schools, whereas in Grades 8 and 9, they are larger for boys than girls for some peer-reported outcomes. The magnitude of the overall effects can be considered practically significant when obtained in a large-scale dissemination of the program.