Stable cell lines expressing high levels of the herpes simplex virus type 1 LAT are refractory to caspase 3 activation and DNA laddering following cold shock induced apoptosis.

TitleStable cell lines expressing high levels of the herpes simplex virus type 1 LAT are refractory to caspase 3 activation and DNA laddering following cold shock induced apoptosis.
Publication TypeJournal Article
Year of Publication2007
AuthorsCarpenter D, Hsiang C, Brown DJ, Jin L, Osorio N, BenMohamed L, Jones C, Wechsler SL
JournalVirology
Volume369
Issue1
Pagination12-8
Date Published2007 Dec 5
ISSN0042-6822
KeywordsAnimals, Apoptosis, Blotting, Western, Caspase 3, Cell Line, Cell Survival, Cold Temperature, DNA Fragmentation, Herpesvirus 1, Human, Mice, MicroRNAs, Neurons, Viral Proteins
Abstract

The herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) gene's anti-apoptosis activity plays a central, but not fully elucidated, role in enhancing the virus's reactivation phenotype. In transient transfection experiments, LAT increases cell survival following an apoptotic insult in the absence of other HSV-1 genes. However, the high background of untransfected cells has made it difficult to demonstrate that LAT inhibits specific apoptotic factors such as caspases. Here we report that, in mouse neuroblastoma cell lines (C1300) stably expressing high levels of LAT, cold shock induced apoptosis was blocked as judged by increased survival, protection against DNA fragmentation (by DNA ladder assay), and inhibition of caspase 3 cleavage and activation (Western blots). To our knowledge, this is the first report providing direct evidence that LAT blocks two biochemical hallmarks of apoptosis, caspase 3 cleavage and DNA laddering, in the absence of other HSV-1 gene products.

Alternate JournalVirology