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

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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