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

Authors

Dale Carpenter, University of California Irvine
Chinhui Hsiang, University of California Irvine
Donald J. Brown, University of California Irvine
Ling Jin, University of California Irvine
Nelson Osorio, University of California Irvine, School of Medicine, Irvine, CA
Lbachir BenMohamed, University of California Irvine
Clinton J. Jones, University of Nebraska - LincolnFollow
Steven L. Wechsler, University of California Irvine

Date of this Version

December 2007

Comments

Published in Virology 369:1 (December 5, 2007), pp. 12-18; doi:10.1016/j.virol.2007.07.023 Copyright © 2007 Elsevier Inc. Used by permission. http://www.sciencedirect.com/science/journal/00426822

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).