Document 3307 DOCN M94A3307 TI Regulation of HIV by retinoic acid (RA) correlates with expression of RA receptors. DT 9412 AU Yamaguchi K; Groopman JE; Byrn RA; Division of Hematology/Oncology, New England Deaconess Hospital,; Bostron, MA 02215. SO Int Conf AIDS. 1994 Aug 7-12;10(1):106 (abstract no. PA0042). Unique Identifier : AIDSLINE ICA10/94369268 AB OBJECTIVE: Analyze the effect of retinoic acids (RA) on human immunodeficiency virus type 1 (HIV-1) expression and correlate this effect with levels of retinoic acid receptor expression in T-lymphoid and monocytoid cell lines. METHODS: The effect of all-trans retinoic acid and 9-cis retinoic acid on HIV-1 production in T-lymphoid (H9,CEM) and monocytoid (U937,THP-1) cell lines was measured during acute and chronic infection. The expression levels of human retinoic acid receptor (hRAR alpha, the receptor for all-trans RA) and the human retinoid-X receptor (hRXR alpha, the receptor for 9-cis RA) were determined by Northern blot analysis. RESULTS: Both all-trans RA and 9-cis RA inhibited virus replication in HIV-1 IIIB infected monocytoid cells, both in the presence and absence of the co-stimulatory agent PMA. The retinoids had weak stimulatory effects, or no effects, on HIV production by T cell lines. HIV production by PMA-stimulated T cell lines was inhibited by these retinoids. 9-cis RA was generally more effective than all-trans RA in inhibiting HIV production and both agents in combination were generally more effective than the single agents alone. hRAR alpha was expressed in H9, U937 and THP-1 cells, but almost undetectable in CEM cells. hRXR alpha was significantly expressed in U937 and THP-1 cells, weakly expressed in H9 cells and not detectable in CEM cells. After stimulation by PMA, hRXR alpha expression increased in H9 cells and U937 cells but not CEM cells. hRAR alpha expression was unchanged in H9 and CEM cells, and elevated in U937 cells, after PMA stimulation. DISCUSSION AND CONCLUSIONS: The effect of retinoic acids on HIV-1 expression was cell type dependent and partially correlated with cellular expression of RA receptors. Endogenous, or exogenously administered, retinoic acids may have a significant role in HIV regulation. DE Cell Line Human HIV-1/*DRUG EFFECTS/PHYSIOLOGY Monocytes/DRUG EFFECTS/METABOLISM/MICROBIOLOGY Receptors, Cytoplasmic and Nuclear/METABOLISM Receptors, Retinoic Acid/*METABOLISM Stereoisomers T-Lymphocytes/DRUG EFFECTS/METABOLISM/MICROBIOLOGY Tetradecanoylphorbol Acetate/PHARMACOLOGY Tretinoin/CHEMISTRY/METABOLISM/*PHARMACOLOGY Virus Replication/DRUG EFFECTS/PHYSIOLOGY MEETING ABSTRACT SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).