Differential HHV-6A gene expression in T cells and primary human astrocytes based on multi-virus array analysis.
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/10(6) cells) at 5 days post-infection. Differential expression of HHV-6A 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.
Yao
Karen
K
Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mandel
Matthew
M
Akyani
Nahid
N
Maynard
Kristen
K
Sengamalay
Naomi
N
Fotheringham
Julie
J
Ghedin
Elodie
E
Kashanchi
Fatah
F
Jacobson
Steven
S
D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D018792:Encephalitis, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019349:Roseolovirus Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics
D004279:DNA, Viral