The regulation of HIV by retinoic acid correlates with cellular expression of the retinoic acid receptors.
OBJECTIVE
To analyze the effect of retinoic acids (RA) on HIV-1 expression and correlate this effect with expression levels of RA receptors (RARs) in T-lymphoid and monocytoid cell lines.


METHODS
The effect of all-trans and 9-cis RA 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 RAR alpha (hRAR alpha, receptor for all-trans RA) and the human retinoid-X receptor alpha (hRXR alpha receptor for 9-cis RA) were determined by Northern blot analysis.


RESULTS
Both all-trans and 9-cis RA inhibited virus replication in HIV-1 IIIB-infected monocytoid cells, in the presence and absence of the co-stimulatory agent phorbol myristate acetate (PMA). The retinoids had weak or no stimulatory effects on HIV production by T-cell lines. HIV production by PMA-stimulated T-cell lines was inhibited by these retinoids. The 9-cis RA was generally more effective than all-trans RA in inhibiting HIV production and in combination generally more effective than the single agents alone. Human RAR alpha was expressed in H9, U937 and THP-1 cells, but almost undetectable in CEM cells. Human RXR 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, RXR alpha expression increased in H9 and U937 cells but not in CEM cells. Human RAR alpha expression was unchanged in H9 and CEM cells, and elevated in U937 cells, after PMA stimulation.


CONCLUSIONS
The effect of RA on HIV-1 expression was cell-type-dependent and partially correlated with cellular expression of RARs. Endogenous or exogenously administered RA may have a significant role in HIV regulation.
Yamaguchi
K
K
New England Deaconess Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215.
Groopman
J E
JE
Byrn
R A
RA
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000821:virology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D017931:DNA Primers; D012367:RNA, Viral; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate