Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 991-999
Latent Infection and Reactivation of Human Herpesvirus 6 in Two
Novel Myeloid Cell Lines
Masaki Yasukawa,
Hideki Ohminami,
Eiji Sada,
Yoshihiro Yakushijin,
Masahiko Kaneko,
Kohsuke Yanagisawa,
Hidehisa Kohno,
Shiro Bando, and
Shigeru Fujita
From the First Department of Internal Medicine, Ehime University
School of Medicine, Ehime; the Department of Medical Technology, Ehime
Medical College of Health Science, Ehime; the Department of Internal
Medicine, Uwajima City Hospital, Ehime; and the Division of Clinical
Laboratory Medicine, Ehime University Hospital, Ehime, Japan.
It has been reported that reactivation of human herpesvirus-6
(HHV-6) causes a failure of hematopoiesis. To clarify the mechanisms of
bone marrow suppression induced by HHV-6 infection, it is necessary to
establish an in vitro model of HHV-6 infection in hematopoietic progenitor cells. We have established two novel Philadelphia
chromosome-positive myeloid cell lines, SAS413 and SAS527, which
possess different hematologic characteristics and show distinct
susceptibility to infection by HHV-6, from a patient with blast crisis
of chronic myelogenous leukemia (CML). HHV-6 subgroup A (HHV-6A) showed
marked replication in SAS413, forming syncytia and inducing cell lysis in short-term culture. On the other hand, HHV-6A-inoculated SAS527 continued to proliferate without cell lysis and only a few cells showed
HHV-6 antigen expression. In contrast to HHV-6A infection, inoculation
with HHV-6 subgroup B (HHV-6B) did not induce any cytopathic
effect (CPE) or viral antigen expression in either of the cell
lines. Although HHV-6B replication was undetectable, the presence of
the HHV-6 genome in both cell lines was shown by polymerase chain
reaction (PCR) during culture for more than 10 months, suggesting that
HHV-6B latently infected SAS413 and SAS527. Phorbol ester treatment of
SAS527 latently infected with HHV-6B resulted in reactivation of HHV-6,
as shown by the appearance of a CPE, positive reactivity for the HHV-6
antigen, and isolation of infectious HHV-6. These novel cell lines
should be useful for studying the mechanisms of HHV-6-induced
hematopoietic failure and HHV-6 latency and reactivation, as well as
differentiation, of the myeloid cell lineage.
