Herpes simplex virus immediate-early protein ICP0 is targeted by SIAH-1 for proteasomal degradation.

Herpes simplex virus (HSV) immediate-early protein ICP0 is a transcriptional activator with E3 ubiquitin ligase activity that induces the degradation of ND10 proteins, including the promyelocytic leukemia protein (PML) and Sp100. Moreover, ICP0 has a role in the derepression of viral genomes and in the modulation of the host interferon response to virus infection. Here, we report that ICP0 interacts with SIAH-1, a cellular E3 ubiquitin ligase that is involved in multiple cellular pathways and is itself capable of mediating PML degradation. This novel virus-host interaction profoundly stabilized SIAH-1 and recruited this cellular E3 ligase into ICP0-containing nuclear bodies. Moreover, SIAH-1 mediated the polyubiquitination of HSV ICP0 in vitro and in vivo. After infection of SIAH-1 knockdown cells with HSV, higher levels of ICP0 were produced, ICP0 was less ubiquitinated, and the half-life of this multifunctional viral regulatory protein was increased. These results indicate an inhibitory role of SIAH-1 during lytic infection by targeting ICP0 for proteasomal degradation.

Measuring success in obesity prevention: a synthesis of Health Promotion Switzerland's long-term monitoring and evaluation strategy.

AIMS: Since 2007, Health Promotion Switzerland has implemented a national priority program for a healthy body weight. This article provides insight into the methodological challenges and results of the program evaluation. METHODS: Evaluation of the long-term program required targeted monitoring and evaluation projects addressing different outcome levels. The evaluation was carried out according to the Swiss Model for Outcome Classification (SMOC), a model designed to classify the effects of health promotion and prevention efforts. RESULTS: The results presented in this article emphasize both content and methods. The national program successfully achieved outcomes on many different levels within complex societal structures. The evaluation system built around the SMOC enabled assessment of program progress and the development of key indicators. However, it is not possible to determine definitively to what extent the national program helped stabilize the prevalence of obesity in Switzerland. CONCLUSION: The model has shown its utility in providing a basis for evaluation and monitoring of the national program. Continuous analysis of data from evaluation and monitoring has made it possible to check the plausibility of suspected causal relationships as well as to establish an overall perspective and assessment of effectiveness supported by a growing body of evidence.