Fachbereich Veterinärmedizin



    Three-dimensional normal human neural progenitor tissue-like assemblies:
    a model of persistent varicella-zoster virus infection (2013)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Goodwin, Thomas J
    McCarthy, Maureen
    Osterrieder, Nikolaus (WE 5)
    Cohrs, Randall J
    Kaufer, Benedikt B (WE 5)
    PLoS Pathogens; 9(8) — S. e1003512
    ISSN: 1553-7366
    URL (Volltext): http://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000018673
    DOI: 10.1371/journal.ppat.1003512
    Pubmed: 23935496
    Institut für Virologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
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    Abstract / Zusammenfassung

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.