Abstract
A few studies of the morphogenesis of human herpesvirus (HHV) 6 type A and B (HHV-6A, -6B) have been performed using neurogenic, lymphoid, or epithelial cells. When human MT-4 T-lymphotropic virus type I (HTLV-I)-producing lymphoid cells were coinfected with HHV-6B in vitro, viral-specific proteins were clearly detected. We therefore attempted to detect virus particles at the ultrastructural level, focusing on the morphogenesis of such particles. Ultrastructurally, HHV-6B virus particles could be observed in the nuclei, cytoplasm, and extracellular spaces of MT-4 cells, in addition to extracellular HTLV-I particles of C type. In the nuclei, dense-cored or doughnut-shaped viral capsids were found, as well as peculiar tubular rods. When budding to perinuclear spaces, these intranuclear capsids exhibited a thin tegument on their surfaces. Distinct teguments were found in the intracytoplasmic particles, which budded into cytoplasmic vacuoles during the process of maturation. The mature particles were detected in the extracellular spaces and the intracytoplasmic vacuoles, with a distinct tegument and surface spikes. An electron-dense layer in the outer part of the tegument was found in some mature particles located in the extracellular space, but no such layer was detected in mature particles in intracytoplasmic vacuoles. No annulate lamellae, but intranuclear tubular rods, were found in the cytoplasm of MT-4 cells. These observations indicate that HHV-6B in MT-4 cells is similar to HHV-6A in fine structure, but differs from HHV-7 and HHV-8 in ultrastructural characteristics. Further comparisons of HHV-6B with HHV-6A, HHV-7, and HHV-8 are needed with regard to functional activity.
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Salahuddin SZ, Ablashi DV, Markhaham PD, Josephs SF, Sturzenegger S, Kaplan M, Hallingan G, Biberfeld P, Wong-Staal F, Kramarsky B, Gallo RC (1986) Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 234: 596–601
Lopez C, Pellet PE, Stewart J, Goldstmith C, Sanderlin K, Black J, Warfield D, Feorino P (1988) Characteristics of human herpesvirus 6. J Infect Dis 157:1271–1273
Albright AV, Lavi E, Black JB, Goldberg S, O’Connor MJ, Gonzalez-Scarano F (1998) The effect of human herpesvirus-6 (HHV-6) on cultured human neural cells: oligodendrocytes and microglia. J Neurovirol 4:486–494
Hall CB, Caserta MT, Schnabel KC, Long C, Epstein LG, Insel RA, Dewhurst S (1998) Persistence of human herpesvirus 6 according to site and variant: possible greater neurotropism of variant A. Clin Infect Dis 26:132–137
Ahlqvist J, Donati D, Martinelli E, Akhyani N, Hou J, Major EO, Jacobson S, Fogdell-Hahn A (2006) Complete replication cycle and acquisition of tegument in nucleus of human herpesvirus 6A in astrocytes and in T-cells. J Med Virol 78:1542–1453
Ahlqvist J, Fotheringham J, Akhyani N, Yao K, Fogdell-Hahn A, Jacobson S (2005) Differential tropism of human herpesvirus 6 (HHV-6) variants and induction of latency by HHV-6A in oligodendrocytes. J Neurovirol 11:384–394
Grivel JC, Santoro F, Chen S, Faga G, Malnati MS, Ito Y, Margolis L, Lusso P (2003) Pathogenic effects of human herpesvirus 6 in human lymphoid tissue ex vivo. J Virol 77:8280–8289
Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y, Kurata T (1994) Identification of human herpesvirus-6 as a causal agent for exanthema subitum. Lancet 344:830
Daibata M, Taguchi T, Taguchi H, Miyoshi I (1998) Integration of human herpesvirus 6 in a Burkitt’s lymphoma cell line. Br J Hematol 102:1307–1313
Nii S, Yoshida M, Uno F, Kurata T, Ikuta K, Yamanishi K (1990) Replication of human herpesvirus 6 (HHV-6): morphological aspects. Adv Exp Med Biol 278:19–28
Takasaki T, Ohkawa N, Sano K, Morimatsu S, Nakano T, Nakai M, Yamaguchi J, Kurane I (1997) Electron microscopic study of human herpesvirus 6-infected human T cell lines superinfected with human immunodeficiency virus type 1. Acta Virol 41:221–229
Dominguez G, Dambaugh TR, Stamey FR, Dewhurst S, Inoue N, Pellett PE (1999) Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A. J Virol 73:8040–8052
Biberfeld P, Kramarsky B, Salahuddin SZ, Gallo RC (1987) Ultrastructural characterization of a new B lymphotropic DNA virus (human herpesvirus 6) isolated from patients with lymphoproliferative disease. J Natl Cancer Inst 79:933–941
Roffman E, Albert J, Goff J, Frenkel N (1990) Putative site for the acquisition of human herpesvirus 6 virion tegument. J Virol 64:6308–6313
Klussmann JP, Krueger E, Sloots T, Berneman Z, Arnold G, Krueger GR (1997) Ultrastructural study of human herpesvirus-7 replication in tissue culture. Virchows Arch 430:417–426
Ohtsuki Y, Iwata J, Furihata M, Takeuchi T, Sonobe H, Miyoshi I (1999) Ultrastructure of Kaposi’s sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) in a primary effusion lymphoma cell line treated with tetradecanoyl phorbol acetate (TPA). Med Electron Microsc 32:94–99
Asada H, Yalcin S, Balachandra K, Higashi K, Yamanishi K (1989) Establishment of titration system for human herpesvirus 6 and evaluation of neutralizing antibody response to the virus. J Clin Microbiol 27:2204–2207
Miyoshi I, Taguchi H, Kubonishi I, Yoshimoto S, Ohtsuki Y, Shiraishi Y, Akagi T (1982) Type C virus-producing cell lines derived from adult T cell leukemia. Gann Monogr Cancer Res 28:219–228
Bandobashi K, Daibata M, Kamioka M, Tanaka Y, Kubonishi I, Taguchi H, Ohtsuki Y, Miyoshi M (1997) Human herpesvirus 6 (HHV-6)-positive Burkitt’s lymphoma: establishment of a novel cell line infected with HHV-6. Blood 90:1200–1207
Pellett PE, Sanchez-Martinez D, Dominguez G, Black JB, Anton E, Greenamoyer C, Dambaugh TR (1993) A strongly immunoreactive virion protein of human herpesvirus 6 variant strain Z29: identification and characterization of the gene and mapping of a variant-specific monoclonal antibody reactive epitope. Virology 195:521–531
Dietrich J, Blumberg BM, Roshal M, Baker JV, Hurley SD (2004) Infection with an endemic human herpesvirus disrupts critical glial precursor cell properties. J Neurosci 24:4875–4883
De Bolle L, Van Loon J, De Clercq E, Naesens L (2005) Quantitative analysis of human herpesvirus 6 cell tropism. J Med Virol 75:76–85
Torrisi MR, Gentile M, Cardinali G, Cirone M, Zompetta C, Lotti LV, Frati L, Faggioni A (1999) Intracellular transport and maturation pathway of human herpesvirus 6. Virology 257:460–471
Oster B, Bundgaard B, Hollsberg P (2005) Human herpesvirus 6B induces cell cycle arrest concomitant with p53 phosphorylation and accumulation in T cells. J Virol 79:1961–1965
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Ohtsuki, Y., Daibata, M., Bandobashi, K. et al. Ultrastructural study of the morphogenesis of human herpesvirus 6 type B in human T-lymphotropic virus type I-producing lymphoid cells. Med Mol Morphol 41, 204–210 (2008). https://doi.org/10.1007/s00795-008-0413-z
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DOI: https://doi.org/10.1007/s00795-008-0413-z