Suppressive effects of human herpesvirus-6 on thrombopoietin-inducible megakaryocytic colony formation in vitro

Hiroki Isomura, Mariko Yoshida, Hikaru Nanba, Nobukiyo Fujiwara, Reiko Ohuchi, Fumio Uno, Megumi Oda, Yoshiki Seino, Masao Yamada

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Two clinical observations, the association of human herpesvirus-6 (HHV-6) with delayed engraftment after stem cell transplantation and thrombocytopenia concomitant with exanthema subitum, prompted us to evaluate the suppressive effects of HHV-6 on thrombopoiesis in vitro. Different culture conditions for thrombopoietin (TPO)-inducible colonies in semi-solid matrices were examined. Using cord blood mononuclear cells as the source of haematopoietic progenitors, two types of colonies, megakaryocyte colony-forming units (CFU-Meg) and non-CFU-Meg colonies, were established. The former colonies were identified by the presence of cells with translucent cytoplasm and highly refractile cell membrane, most of which were positive for the CD41 antigen. Although the plating efficiency of both types was much higher under serum-containing conditions than under serum-free conditions, the proportion of CFU-Meg to non-CFU-Meg colonies was consistently higher under serum-free conditions. The plating efficiency of CFU-Meg colonies was doubled by adding stem cell factor to the serum-free matrix. The effects of two variants of HHV-6 (HHV-6A and 6B) and human herpesvirus-7 (HHV-7) on TPO-inducible colonies were then compared. HHV-6B inhibited both CFU-Meg and non-CFU-Meg colony formation under serum-free and serum-containing conditions. HHV-6A had similar inhibitory effects. In contrast, HHV-7 had no effect on TPO-inducible colony formation. Heat-inactivation and ultra-filtration of the virus sample completely abolished the suppressive effect. After infection of CD34+ cells with HHV-6, the viral genome was consistently detected by in situ hybridization. These data suggest that the direct effect of HHV-6 on haematopoietic progenitors is one of the major causes of the suppression of thrombopoiesis.

Original languageEnglish
Pages (from-to)663-673
Number of pages11
JournalJournal of General Virology
Volume81
Issue number3
Publication statusPublished - 2000

Fingerprint

Human Herpesvirus 6
Thrombopoietin
Human Herpesvirus 7
Serum
Thrombopoiesis
Exanthema Subitum
Platelet Membrane Glycoprotein IIb
In Vitro Techniques
Stem Cell Factor
Megakaryocytes
Viral Genome
Stem Cell Transplantation
Fetal Blood
Thrombocytopenia
In Situ Hybridization
Blood Cells
Cytoplasm
Stem Cells
Hot Temperature
Cell Membrane

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Suppressive effects of human herpesvirus-6 on thrombopoietin-inducible megakaryocytic colony formation in vitro. / Isomura, Hiroki; Yoshida, Mariko; Nanba, Hikaru; Fujiwara, Nobukiyo; Ohuchi, Reiko; Uno, Fumio; Oda, Megumi; Seino, Yoshiki; Yamada, Masao.

In: Journal of General Virology, Vol. 81, No. 3, 2000, p. 663-673.

Research output: Contribution to journalArticle

Isomura, H, Yoshida, M, Nanba, H, Fujiwara, N, Ohuchi, R, Uno, F, Oda, M, Seino, Y & Yamada, M 2000, 'Suppressive effects of human herpesvirus-6 on thrombopoietin-inducible megakaryocytic colony formation in vitro', Journal of General Virology, vol. 81, no. 3, pp. 663-673.
Isomura, Hiroki ; Yoshida, Mariko ; Nanba, Hikaru ; Fujiwara, Nobukiyo ; Ohuchi, Reiko ; Uno, Fumio ; Oda, Megumi ; Seino, Yoshiki ; Yamada, Masao. / Suppressive effects of human herpesvirus-6 on thrombopoietin-inducible megakaryocytic colony formation in vitro. In: Journal of General Virology. 2000 ; Vol. 81, No. 3. pp. 663-673.
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AU - Uno, Fumio

AU - Oda, Megumi

AU - Seino, Yoshiki

AU - Yamada, Masao

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