title: Complete replication cycle and acquisition of tegument in nucleus of human herpesvirus 6A in astrocytes and in T-cells.
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.
authors.affiliation: Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ahlqvist
authors.forename: Donatella
authors.initials: D
authors.lastname: Donati
authors.forename: Elena
authors.initials: E
authors.lastname: Martinelli
authors.forename: Nahid
authors.initials: N
authors.lastname: Akhyani
authors.forename: Jean
authors.initials: J
authors.lastname: Hou
authors.forename: Eugene O
authors.initials: EO
authors.lastname: Major
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
authors.forename: Anna
authors.initials: A
authors.lastname: Fogdell-Hahn
mesh_terms: D001253:Astrocytes / Q000648:ultrastructure / Q000821:virology*; D022003:Cell Nucleus Structures / Q000502:physiology / Q000648:ultrastructure / Q000821:virology*; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D015654:Herpesvirus 6, Human / Q000254:growth & development* / Q000472:pathogenicity / Q000648:ultrastructure; D006801:Humans; D046529:Microscopy, Electron, Transmission; D013601:T-Lymphocytes / Q000648:ultrastructure / Q000821:virology*; D014771:Virion / Q000254:growth & development / Q000648:ultrastructure; D014779:Virus Replication