Differentiating agents facilitate infection of myeloid leukemia cell lines by monocytotropic HIV-1 strains.
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.
Kitano
K
K
Department of Medicine, UCLA School of Medicine 90024-1678.
Baldwin
G C
GC
Raines
M A
MA
Golde
D W
DW
D003994:Bucladesine / Q000494:pharmacology*; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014316:Tritium; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D015704:CD4 Antigens; D004279:DNA, Viral; D014316:Tritium; D014212:Tretinoin; D003994:Bucladesine; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine; D004121:Dimethyl Sulfoxide