Effect of Retinoic Acid on HL-60 Cells Infected With Human Immunodeficiency Virus Type

ELLS OF THE monocyte/macrophage lineage are considered to be a reservoir of human immunodeficiency virus (HIV). The virus infects these cells without killing them and the cells produce moderate amounts of virus indefinitely.' During the maturation of the cells, HIV replication can be modified.' In particular, HL-60 cells induced to differentiate before infection become permissive for monocytotropic strains of HIV type 1' and infection with HIV can modify the capacity of the cells to differentiate in response to inducer^.',^ U937, a monocyte/macrophage cell line, has been studied extensively. Differentiation of these cells upregulates HIV expression at the level of HIV mRNA5 and virus produ~tion.',~ Modification of HIV expression can be mediated by several cytokines: tumor necrosis factor a (TNFa) upregulates HIV replication in a T-cell line and in U937 cell^^.^; the interferons (IFNs) downregulate it.4,7,'0"2 However, IFNy can upregulate HIV replication if added to the culture before infection.13 Transforming growth factor P (TGFP) also has dichotomous effects. If added to differentiating monocytes, it upregulates HIV replication but downregulates it in immature monocytes and modifies HIV replication after induction of the cells with some, but not all, inducer^.'^.'^ Retinoic acid appears to act through TGFP." Turpin et all' report an increase of HIV mRNA transcription in monocytes, the monocyte-like U937, and the myeloid THP-1 cells treated with retinoic acid. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to upregulate HIV expression in U1 cells (a clone derived from U937 cell~), '~*' ' but to downregulate it in the parent line, U937.'" Interleukin1 (IL-I),lq IL-3," and IL-6" can upregulate HIV expression. Upregulation of HIV expression appears to be linked to the activation of protein kinase C,I8 but also to the induction of Differentiation induces the production of cytoC