Herpes simplex virus type 1 latency-associated transcript inhibits apoptosis and promotes neurite sprouting in neuroblastoma cells following serum starvation by maintaining protein kinase B (AKT) levels

Sumin Li, Dale Carpenter, Chinhui Hsiang, Steven L. Wechsler, Clinton Jones

Research output: Contribution to journalArticle

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Abstract

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is expressed abundantly in latently infected sensory neurons. LAT-deletion-mutant virus strains have reducedreactivation phenotypes in small animal models of infection, demonstrating that LAT plays an important role in the latency-reactivation cycle of HSV-1. Previous studies demonstrated that the anti-apoptosis functions of LAT are important for regulating the latency-reactivation cycle because three different anti-apoptosis genes can substitute for LAT. Although LAT inhibits caspase 3 activation, the signalling pathway by which LAT inhibits caspase 3 activation was not identified. In this study, we analysed mouse neuroblastoma cells (C1300) that express LAT stably (DC-LAT6 cells) following serum starvation. As expected, DC-LAT6 cells were resistant to apoptosis following serum withdrawal. Levels of total and phosphorylated AKT (protein kinase B), a serine/threonine protein kinase that promotes cell survival, were higher in DC-LAT6 cells after serum withdrawal than in C1300 cells or a cell line stably transfected with a LAT promoter mutant (DC-DLAT311). A specific AKT inhibitor reduced the anti-apoptosis functions of LAT and phosphorylated AKT levels. After serum withdrawal, more DC-LAT6 cells sprouted neurites and exhibited a differentiated morphology. NeuN (neuronal nuclei), a neuron-specific nuclear protein, was expressed abundantly in DC-LAT6 cells, but not C1300 cells, after serum withdrawal, further supporting the concept that LAT enhanced neuronal-like morphology. Collectively, these studies suggested that LAT, directly or indirectly, maintained total and phosphorylated AKT levels, which correlated with increased cell survival and mature neuronal-like morphology.

Original languageEnglish (US)
Pages (from-to)858-866
Number of pages9
JournalJournal of General Virology
Volume91
Issue number4
DOIs
StatePublished - Apr 1 2010

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Proto-Oncogene Proteins c-akt
Human Herpesvirus 1
Neurites
Starvation
Neuroblastoma
Apoptosis
Serum
Caspase 3
Cell Survival
herpes simplex virus-1 latency associated transcript
Protein-Serine-Threonine Kinases
Sensory Receptor Cells
Nuclear Proteins
Animal Models
Viruses
Phenotype
Neurons
Cell Line
Infection

ASJC Scopus subject areas

  • Virology

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Herpes simplex virus type 1 latency-associated transcript inhibits apoptosis and promotes neurite sprouting in neuroblastoma cells following serum starvation by maintaining protein kinase B (AKT) levels. / Li, Sumin; Carpenter, Dale; Hsiang, Chinhui; Wechsler, Steven L.; Jones, Clinton.

In: Journal of General Virology, Vol. 91, No. 4, 01.04.2010, p. 858-866.

Research output: Contribution to journalArticle

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