The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.
wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Herpes simplex virus type 1 (HSV-1) is one of the most frequent and successful human pathogens.It targets immature dendritic cells (iDCs) to interfere with the antiviral immune response.The mechanisms underlying apoptosis of HSV-1-infected iDCs are not fully understood.Previously, we have shown that HSV-1-induced apoptosis of iDCs is associated with downregulation of the cellular FLICE-inhibitory protein (c-FLIP), a potent inhibitor of caspase-8-mediated apoptosis.In this study, we prove that HSV-1 induces degradation of c-FLIP in a proteasome-independent manner.In addition, by using c-FLIP-specific small interfering RNA (siRNA) we show for the first time that downregulation of c-FLIP expression is sufficient to drive uninfected iDCs into apoptosis, underlining the importance of this molecule for iDC survival.Surprisingly, we also observed virus-induced c-FLIPdownregulation in epithelial cells and many other cell types that do not undergo apoptosis after HSV-1 infection.Microarray analyses revealed that HSV-1-encoded latency-associated transcript (LAT) sequences, which can substitute for c-FLIP as an inhibitor of caspase-8-mediated apoptosis, are much less abundant in iDCs as compared to epithelial cells.Finally, iDCs infected with an HSV-1 LAT knockout mutant showed increased apoptosis when compared to iDCs infected with the corresponding wild-type HSV-1.Taken together, our results demonstrate that apoptosis of HSV-1-infected iDCs requires both c-FLIPdownregulation and diminished expression of viral LAT.