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Variable immortalizing potential and frequent virus latency in blood-
derived T-cell clones infected with human T-cell leukemia virus type I
JH Richardson, P Hollsberg, A Windhagen, LA Child, DA Hafler and AM Lever
Department of Medicine, University of Cambridge, United Kingdom.
Human T-cell leukemia virus type I (HTLV-I)-infected T cells expanded in
vitro by single-cell cloning provide a unique system for investigating
virus-cell interactions in nonimmortalized T cells. By analysis of clones
generated randomly from the blood of virus carriers, we confirm that CD4 T
cells are the major reservoir of HTLV-I in vivo and show that most infected
cells contain a single integrated provirus. Contrary to the situation in
HTLV-I immortalized cell lines, the HTLV-I provirus was found to be
transcriptionally silent in a high proportion of randomly generated T-cell
clones and could not be reactivated by mitogenic stimulation. The
spontaneous proliferation previously documented in HTLV-I-infected T-cell
clones was not observed in silently infected cells, and therefore
correlates directly with the expression of tax and other viral genes. The
only cytokine mRNA found to be significantly elevated in the
virus-producing clones was interleukin-6; however, receptor-blocking
experiments argue against a role for IL-6 in the virus-induced cell
proliferation. We observed a striking variation in the ability of
individual HTLV-I-producing clones to immortalize fresh peripheral blood
lymphocytes. This ability did not correlate with the levels of viral mRNA
expression, gag p24 production, spontaneous proliferation, or
tax-transactivation, possibly suggesting a role for host cell factors as
determinants of viral infectivity or immortalization. Studies to elucidate
the basis of this phenotypic heterogeneity should enhance our understanding
of viral spread and pathogenesis.
Volume 89,
Issue 9,
pp. 3303-3314,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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