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

Research output: Contribution to journalArticle

48 Citations (Scopus)

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

Fingerprint

Human herpesvirus 1
Granzymes
Human Herpesvirus 1
apoptosis
T-lymphocytes
neurons
Apoptosis
T-Lymphocytes
Neurons
Virus Latency
granules
cells
cell culture
Cell Culture Techniques
Phenotype
phenotype
caspase-3
herpes simplex virus-1 latency associated transcript
Cell Extracts
Caspase 3

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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

In: Journal of virology, Vol. 85, No. 5, 01.03.2011, p. 2325-2332.

Research output: Contribution to journalArticle

Jiang, X, Chentoufi, AA, Hsiang, C, Carpenter, D, Osorio, N, BenMohamed, L, Fraser, NW, Jones, C & Wechsler, SL 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, vol. 85, no. 5, pp. 2325-2332. https://doi.org/10.1128/JVI.01791-10
Jiang, Xianzhi ; Chentoufi, Aziz Alami ; Hsiang, Chinhui ; Carpenter, Dale ; Osorio, Nelson ; BenMohamed, Lbachir ; Fraser, Nigel W. ; Jones, Clinton ; Wechsler, Steven L. / 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. In: Journal of virology. 2011 ; Vol. 85, No. 5. pp. 2325-2332.
@article{65fb946dcd50475fb778ec62781190cd,
title = "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",
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.",
author = "Xianzhi Jiang and Chentoufi, {Aziz Alami} and Chinhui Hsiang and Dale Carpenter and Nelson Osorio and Lbachir BenMohamed and Fraser, {Nigel W.} and Clinton Jones and Wechsler, {Steven L.}",
year = "2011",
month = "3",
day = "1",
doi = "10.1128/JVI.01791-10",
language = "English (US)",
volume = "85",
pages = "2325--2332",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - 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

AU - Jiang, Xianzhi

AU - Chentoufi, Aziz Alami

AU - Hsiang, Chinhui

AU - Carpenter, Dale

AU - Osorio, Nelson

AU - BenMohamed, Lbachir

AU - Fraser, Nigel W.

AU - Jones, Clinton

AU - Wechsler, Steven L.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79551719108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551719108&partnerID=8YFLogxK

U2 - 10.1128/JVI.01791-10

DO - 10.1128/JVI.01791-10

M3 - Article

C2 - 21177822

AN - SCOPUS:79551719108

VL - 85

SP - 2325

EP - 2332

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 5

ER -