Induction of monocytic differentiation and NF-kappa B-like activities by human immunodeficiency virus 1 infection of myelomonoblastic cells.
The effects of human immunodeficiency virus 1 (HIV-1) infection on cellular differentiation and NF-kappa B DNA binding activity have been investigated in a new model of myeloid differentiation. PLB-985 cells represent a bipotential myelomonoblastic cell population capable of either granulocytic or monocytic differentiation after induction with appropriate inducers. By virtue of the presence of CD4 on the cell surface, PLB-985 cells were chronically infected with HIV-1 strain IIIB. PLB-IIIB cells clearly possessed a more monocytic phenotype than the parental myeloblasts, as determined by differential staining, increased expression of the myeloid-specific surface markers, and transcription of the c-fms proto-oncogene. NF-kappa B binding activity was inducible by tumor necrosis factor and phorbol myristate acetate in PLB-985. However, in PLB-IIIB cells, constitutive expression of a novel NF-kappa B complex was detected, composed of proteins ranging between 70 and 110 kD. These proteins interacted specifically with the symmetric NF-kappa B site from the interferon beta (IFN-beta) promoter. Mutations affecting the 5' guanine residues of the kappa B site were unable to compete for these NF-kappa B-related proteins. Inducibility of endogenous IFN-beta and IFN-alpha RNA was also increased in PLB-IIIB cells. These studies indicate that HIV-1 infection of myelomonoblastic cells may select for a more mature monocytic phenotype and that unique subunit associations of NF-kappa B DNA binding proteins may contribute to differential NF-kappa B-mediated gene expression.
Roulston
A
A
Lady Davis Institute for Medical Research, Quebec, Canada.
D'Addario
M
M
Boulerice
F
F
Caplan
S
S
Wainberg
M A
MA
Hiscott
J
J
D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology*; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology / Q000382:microbiology; D001854:Bone Marrow Cells; D015704:CD4 Antigens / Q000032:analysis; D002454:Cell Differentiation; D015870:Gene Expression; D016236:Genes, fms / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D015497:HIV-1; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014775:Virus Activation
D015704:CD4 Antigens; D016898:Interferon-alpha; C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D016899:Interferon-beta