Complete replication cycle and acquisition of tegument in nucleus of human herpesvirus 6A in astrocytes and in T-cells

Authors

  • Jenny Ahlqvist,

    1. Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
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  • Donatella Donati,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    Current affiliation:
    1. Dipartimento di Biologia Molecolare, Sezione di Virologia Universita' di Siena, Siena, Italy.
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  • Elena Martinelli,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    Current affiliation:
    1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
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  • Nahid Akhyani,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
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  • Jean Hou,

    1. Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
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  • Eugene O. Major,

    1. Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
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  • Steven Jacobson,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
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  • Anna Fogdell-Hahn

    Corresponding author
    1. Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
    • Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden.
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  • Steven Jacobson and Anna Fogdell-Hahn shared senior authorship.

Abstract

The ultrastructural replication cycle of human herpesvirus 6A and 6B, both T-lymphotropic viruses, with tropism for the central nervous system, was compared by electron microscopy in the same cells, that is, in the T-lymphoblastoid cell line SupT-1 and in human astrocytes. Both HHV-6A and HHV-6B replicated efficiently in SupT-1 and formed viral particles. The tegument is the least characterized structure of the herpesviral particle and both variants were able to form intranuclear membrane compartments called tegusomes in SupT-1 where tegumentation occurred. Also, tegumentation occurred in HHV-6A infected cells in the nucleoplasm without the presence of a tegusome. This suggests that there is more than one possible route of tegumentation. Differences in the replication cycles between HHV-6A and HHV-6B were also observed in the cytoplasm. One such difference was that prominent annulate lamellae were only found in the cytoplasm of HHV-6A infected cells. In astrocytes a successful formation of viral particles was only seen with the HHV-6A variant. The HHV-6A virus life cycle in astrocytes resembled the life cycle in the T-cell line SupT-1, except that no annulate lamellae were found. Complete viral particles were found extracellularly around the astrocytes and the supernatant of infected astrocytes were able to re-infect SupT-1 cells. This suggests that HHV-6A infection in astrocytes can generate complete, viable, and infectious viral particles. The HHV-6 variants behave differently in the same type of cells and have different tropisms for astrocytes, supporting the notion that the variants might induce different diseases. J. Med. Virol. 78:1542–1553, 2006. © 2006 Wiley-Liss, Inc.

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