Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis

Karen Yao, Matthew Mandel, Nahid Akyani, Kristen Maynard, Naomi Sengamalay, Julie Fotheringham, Elodie Ghedin, Fatah Kashanchi, Steven Jacobson

Research output: Contribution to journalArticle

Abstract

Human herpesvirus 6 (HHV-6) is a ubiquitous virus that has been associated with a wide spectrum of diseases, such as exanthem infantum, multiple sclerosis, seizures, encephalitis/meningitis, and more recently, mesial temporal lobe sclerosis. Although HHV-6 is known to predominately infect CD4+ T lymphocytes, its ability to infect neural glial cells has been demonstrated both in vitro and in vivo. Reactivation of latent HHV-6 infection in the brain has recently been suggested to play a role in the development of neuropathogenesis. To investigate the association of viral gene expression and disease pathogenesis, we developed a multi-virus array containing all open reading frames of the HHV-6 virus and other pathogenically related viruses (EBV, HBV, HHV-8, HIV-1, HTLV-1, HTLV-2) to study expression of viral gene transcripts. In this study, we infected CD4+ T lymphocytes and primary human astrocytes derived from brain biopsy material in vitro with the more neurotropic HHV-6A strain. Hierarchal cluster analysis based on gene expression over time suggested a temporally regulated herpesvirus transcription process. Furthermore, we compared viral gene expression in CD4+ T lymphocytes and primary human astrocytes at peak viral load levels (> 10 8 copies of virus/106 cells) at 5 days post-infection. Differential expression of HHV-6 A genes was observed between CD4+ T lymphocytes and primary human astrocytes. Absence of a number of HHV-6 genes detected at 5 days post-infection in primary human astrocytes suggests an alternative replication strategy used by HHV-6 to evade immune detection and allow establishment of persistent infection in neural glial cells.

Original languageEnglish (US)
Pages (from-to)789-798
Number of pages10
JournalGLIA
Volume53
Issue number8
DOIs
StatePublished - Jun 2006

Fingerprint

Human Herpesvirus 6
Astrocytes
Viruses
T-Lymphocytes
Gene Expression
Viral Genes
Neuroglia
Infection
vif Genes
Human T-lymphotropic virus 2
Herpesviridae Infections
Human Herpesvirus 8
Human T-lymphotropic virus 1
Herpesviridae
Brain
Sclerosis
Virus Diseases
Encephalitis
Temporal Lobe
Exanthema

Keywords

  • Astrocytes
  • HHV-6
  • Multi-virus array
  • Multiple sclerosis
  • Viral persistency

ASJC Scopus subject areas

  • Immunology

Cite this

Yao, K., Mandel, M., Akyani, N., Maynard, K., Sengamalay, N., Fotheringham, J., ... Jacobson, S. (2006). Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis. GLIA, 53(8), 789-798. https://doi.org/10.1002/glia.20333

Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis. / Yao, Karen; Mandel, Matthew; Akyani, Nahid; Maynard, Kristen; Sengamalay, Naomi; Fotheringham, Julie; Ghedin, Elodie; Kashanchi, Fatah; Jacobson, Steven.

In: GLIA, Vol. 53, No. 8, 06.2006, p. 789-798.

Research output: Contribution to journalArticle

Yao, K, Mandel, M, Akyani, N, Maynard, K, Sengamalay, N, Fotheringham, J, Ghedin, E, Kashanchi, F & Jacobson, S 2006, 'Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis', GLIA, vol. 53, no. 8, pp. 789-798. https://doi.org/10.1002/glia.20333
Yao K, Mandel M, Akyani N, Maynard K, Sengamalay N, Fotheringham J et al. Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis. GLIA. 2006 Jun;53(8):789-798. https://doi.org/10.1002/glia.20333
Yao, Karen ; Mandel, Matthew ; Akyani, Nahid ; Maynard, Kristen ; Sengamalay, Naomi ; Fotheringham, Julie ; Ghedin, Elodie ; Kashanchi, Fatah ; Jacobson, Steven. / Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis. In: GLIA. 2006 ; Vol. 53, No. 8. pp. 789-798.
@article{071dbe46a28b420eab226a62b0dcafe0,
title = "Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis",
abstract = "Human herpesvirus 6 (HHV-6) is a ubiquitous virus that has been associated with a wide spectrum of diseases, such as exanthem infantum, multiple sclerosis, seizures, encephalitis/meningitis, and more recently, mesial temporal lobe sclerosis. Although HHV-6 is known to predominately infect CD4+ T lymphocytes, its ability to infect neural glial cells has been demonstrated both in vitro and in vivo. Reactivation of latent HHV-6 infection in the brain has recently been suggested to play a role in the development of neuropathogenesis. To investigate the association of viral gene expression and disease pathogenesis, we developed a multi-virus array containing all open reading frames of the HHV-6 virus and other pathogenically related viruses (EBV, HBV, HHV-8, HIV-1, HTLV-1, HTLV-2) to study expression of viral gene transcripts. In this study, we infected CD4+ T lymphocytes and primary human astrocytes derived from brain biopsy material in vitro with the more neurotropic HHV-6A strain. Hierarchal cluster analysis based on gene expression over time suggested a temporally regulated herpesvirus transcription process. Furthermore, we compared viral gene expression in CD4+ T lymphocytes and primary human astrocytes at peak viral load levels (> 10 8 copies of virus/106 cells) at 5 days post-infection. Differential expression of HHV-6 A genes was observed between CD4+ T lymphocytes and primary human astrocytes. Absence of a number of HHV-6 genes detected at 5 days post-infection in primary human astrocytes suggests an alternative replication strategy used by HHV-6 to evade immune detection and allow establishment of persistent infection in neural glial cells.",
keywords = "Astrocytes, HHV-6, Multi-virus array, Multiple sclerosis, Viral persistency",
author = "Karen Yao and Matthew Mandel and Nahid Akyani and Kristen Maynard and Naomi Sengamalay and Julie Fotheringham and Elodie Ghedin and Fatah Kashanchi and Steven Jacobson",
year = "2006",
month = "6",
doi = "10.1002/glia.20333",
language = "English (US)",
volume = "53",
pages = "789--798",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "8",

}

TY - JOUR

T1 - Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis

AU - Yao, Karen

AU - Mandel, Matthew

AU - Akyani, Nahid

AU - Maynard, Kristen

AU - Sengamalay, Naomi

AU - Fotheringham, Julie

AU - Ghedin, Elodie

AU - Kashanchi, Fatah

AU - Jacobson, Steven

PY - 2006/6

Y1 - 2006/6

N2 - Human herpesvirus 6 (HHV-6) is a ubiquitous virus that has been associated with a wide spectrum of diseases, such as exanthem infantum, multiple sclerosis, seizures, encephalitis/meningitis, and more recently, mesial temporal lobe sclerosis. Although HHV-6 is known to predominately infect CD4+ T lymphocytes, its ability to infect neural glial cells has been demonstrated both in vitro and in vivo. Reactivation of latent HHV-6 infection in the brain has recently been suggested to play a role in the development of neuropathogenesis. To investigate the association of viral gene expression and disease pathogenesis, we developed a multi-virus array containing all open reading frames of the HHV-6 virus and other pathogenically related viruses (EBV, HBV, HHV-8, HIV-1, HTLV-1, HTLV-2) to study expression of viral gene transcripts. In this study, we infected CD4+ T lymphocytes and primary human astrocytes derived from brain biopsy material in vitro with the more neurotropic HHV-6A strain. Hierarchal cluster analysis based on gene expression over time suggested a temporally regulated herpesvirus transcription process. Furthermore, we compared viral gene expression in CD4+ T lymphocytes and primary human astrocytes at peak viral load levels (> 10 8 copies of virus/106 cells) at 5 days post-infection. Differential expression of HHV-6 A genes was observed between CD4+ T lymphocytes and primary human astrocytes. Absence of a number of HHV-6 genes detected at 5 days post-infection in primary human astrocytes suggests an alternative replication strategy used by HHV-6 to evade immune detection and allow establishment of persistent infection in neural glial cells.

AB - Human herpesvirus 6 (HHV-6) is a ubiquitous virus that has been associated with a wide spectrum of diseases, such as exanthem infantum, multiple sclerosis, seizures, encephalitis/meningitis, and more recently, mesial temporal lobe sclerosis. Although HHV-6 is known to predominately infect CD4+ T lymphocytes, its ability to infect neural glial cells has been demonstrated both in vitro and in vivo. Reactivation of latent HHV-6 infection in the brain has recently been suggested to play a role in the development of neuropathogenesis. To investigate the association of viral gene expression and disease pathogenesis, we developed a multi-virus array containing all open reading frames of the HHV-6 virus and other pathogenically related viruses (EBV, HBV, HHV-8, HIV-1, HTLV-1, HTLV-2) to study expression of viral gene transcripts. In this study, we infected CD4+ T lymphocytes and primary human astrocytes derived from brain biopsy material in vitro with the more neurotropic HHV-6A strain. Hierarchal cluster analysis based on gene expression over time suggested a temporally regulated herpesvirus transcription process. Furthermore, we compared viral gene expression in CD4+ T lymphocytes and primary human astrocytes at peak viral load levels (> 10 8 copies of virus/106 cells) at 5 days post-infection. Differential expression of HHV-6 A genes was observed between CD4+ T lymphocytes and primary human astrocytes. Absence of a number of HHV-6 genes detected at 5 days post-infection in primary human astrocytes suggests an alternative replication strategy used by HHV-6 to evade immune detection and allow establishment of persistent infection in neural glial cells.

KW - Astrocytes

KW - HHV-6

KW - Multi-virus array

KW - Multiple sclerosis

KW - Viral persistency

UR - http://www.scopus.com/inward/record.url?scp=33646509004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646509004&partnerID=8YFLogxK

U2 - 10.1002/glia.20333

DO - 10.1002/glia.20333

M3 - Article

VL - 53

SP - 789

EP - 798

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 8

ER -