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.
Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Karen
K
Yao
Matthew
M
Mandel
Nahid
N
Akyani
Kristen
K
Maynard
Naomi
N
Sengamalay
Julie
J
Fotheringham
Elodie
E
Ghedin
Fatah
F
Kashanchi
Steven
S
Jacobson
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