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

Dale Carpenter, Chinhui Hsiang, Donald J. Brown, Ling Jin, Nelson Osorio, Lbachir BenMohamed, Clinton Jones, Steven L. Wechsler

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalVirology
Volume369
Issue number1
DOIs
StatePublished - Dec 5 2007

Keywords

  • Apoptosis
  • HSV-1
  • LAT
  • Latency
  • Latency associated transcript

ASJC Scopus subject areas

  • Virology

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