title: Viral activation from latency during retrodifferentiation of U937 cells exposed to phorbol ester followed by infection with human immunodeficiency virus type 1.
abstract: To determine the mechanism underlying the human immunodeficiency virus type 1 (HIV-1) latency and its activation in monocyte/macrophage lineage, the human promonocytic cell line U937 was infected with HIV-1 after differentiation with varied doses of phorbol 12-myristate 13-acetate (PMA). Variously differentiated intermediate stages were generated in U937 cells in a dose-dependent manner. When these cells were infected with lymphotropic HIV-1, the kinetics of the production of HIV-1 DNA, the appearance of HIV-1 antigen-positive cells, and viral production in the conditioned media were slower at higher doses of PMA. This different susceptibility to the infection was not due to the rate of HIV-1 adsorption. Viral replication from latency in the differentiated cells was activated in proportion with the retrodifferentiation observed in long-term cultures of the host cells. Thus, our data demonstrate the close correlation between the regulation of HIV-1 replication and the differentiation stage of monocyte/macrophage lineage cells at the time of HIV-1 infection. The retrodifferentiation phenomenon in infected cells seems to be particularly important for understanding the mechanisms for HIV-1 activation from latency.
authors.affiliation: Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Kameoka
authors.forename: M
authors.initials: M
authors.lastname: Kishi
authors.forename: I
authors.initials: I
authors.lastname: Azuma
authors.forename: K
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D001483:Base Sequence; D015704:CD4 Antigens / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007948:Leukemia, Monocytic, Acute / Q000276:immunology / Q000821:virology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000821:virology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014775:Virus Activation / Q000187:drug effects / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D013755:Tetradecanoylphorbol Acetate