The herpes simplex virus type 1 latency-associated transcript can protect neuron-derived C1300 and neuro2A cells from granzyme B-induced apoptosis and CD8 T-cell killing

Xianzhi Jiang, Aziz Alami Chentoufi, Chinhui Hsiang, Dale Carpenter, Nelson Osorio, Lbachir BenMohamed, Nigel W. Fraser, Clinton Jones, Steven L. Wechsler

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50 Scopus citations

Abstract

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is the only HSV-1 gene transcript abundantly expressed throughout latency. LAT null mutants have a significantly reduced reactivation phenotype. LAT's antiapoptosis activity is the major LAT factor involved in supporting the wild-type reactivation phenotype. During HSV-1 latency, some ganglionic neurons are surrounded by CD8 T cells, and it has been proposed that these CD8 T cells help maintain HSV-1 latency by suppressing viral reactivations. Surprisingly, despite injection of cytotoxic lytic granules by these CD8 T cells into latently infected neurons, neither apoptosis nor neuronal cell death appears to occur. We hypothesized that protection of latently infected neurons against cytotoxic CD8 T-cell killing is due to LAT's antiapoptosis activity. Since CD8 T-cell cytotoxic lytic granule-mediated apoptosis is critically dependent on granzyme B (GrB), we examined LAT's ability to block GrB-induced apoptosis. We report here that (i) LAT can interfere with GrB-induced apoptosis in cell cultures, (ii) LAT can block GrB-induced cleavage (activation) of caspase-3 both in cell culture and in a cell-free in vitro cell extract assay, and (iii) LAT can protect C1300 and Neuro2A cells from cytotoxic CD8 T-cell killing in vitro. These findings support the hypothesis that LAT's antiapoptosis activity can protect latently infected neurons from being killed by CD8 T-cell lytic granules in vivo.

Original languageEnglish (US)
Pages (from-to)2325-2332
Number of pages8
JournalJournal of virology
Volume85
Issue number5
DOIs
StatePublished - Mar 1 2011

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Jiang, X., Chentoufi, A. A., Hsiang, C., Carpenter, D., Osorio, N., BenMohamed, L., Fraser, N. W., Jones, C., & Wechsler, S. L. (2011). The herpes simplex virus type 1 latency-associated transcript can protect neuron-derived C1300 and neuro2A cells from granzyme B-induced apoptosis and CD8 T-cell killing. Journal of virology, 85(5), 2325-2332. https://doi.org/10.1128/JVI.01791-10