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Differentiating agents facilitate infection of myeloid leukemia cell lines
by monocytotropic HIV-1 strains [published erratum appears in Blood 1991
Apr 1;77(7):1624]
K Kitano, GC Baldwin, MA Raines and DW Golde
Department of Medicine, UCLA School of Medicine 90024-1678.
Monocytotropic human immunodeficiency virus type 1 (HIV-1) isolates from
patients with acquired immunodeficiency syndrome (AIDS) infect mononuclear
phagocytes as well as activated T cells, but do not usually infect immature
human myeloid cell lines in vitro. The HL-60 promyelocytic/myeloblastic
cell line and the promonocytic line, U937, were susceptible to productive
infection by monocytotropic HIV-1 isolates (HIV-1JR-FL and HTLV-IIIBa-L)
after treatment with retinoic acid, dimethyl sulfoxide, dibutyryl cAMP,
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), or
12-O-tetradecanoyl-phorbol-13-acetate (TPA). Virus production was only
detected when these compounds were added before virus infection. Virus
replication did not correlate with CD4 receptor expression because
undifferentiated HL-60 cells express CD4 and the level of CD4 expression
did not increase after differentiation in the presence of retinoic acid,
1,25(OH)2D3, or TPA. A mature monocytic cell line (THP-1) was capable of
infection without pretreatment, and treatment with differentiating agents
enhanced virus production. A chronically infected cell line (J-HL-60) was
isolated after HIV-1JR-FL infection of HL-60 cells treated with retinoic
acid. Virus production in this cell line was enhanced more than 10-fold
after differentiation in the presence of 1,25(OH)2D3 or TPA. The majority
of virus production by 1,25(OH)2D3-treated J-HL-60 cells was associated
with the mature, adherent population. Molecular analysis of a cloned line
of J-HL-60 showed integration of a single DNA provirus. These results
suggest that cellular factors associated with precursor cell
differentiation along the myelomonocytic pathway are required for optimal
replication of monocytotropic HIV-1 strains in vitro.
Volume 76,
Issue 10,
pp. 1980-1988,
11/15/1990
Copyright © 1990 by The American Society of Hematology
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