0 3 The the DT 4 14 regulation regulation NN 15 17 of of IN 18 21 HIV HIV NNP 22 24 by by IN 25 33 retinoic retinoic JJ 34 38 acid acid NN 39 49 correlates correlate VBZ 50 54 with with IN 55 63 cellular cellular JJ 64 74 expression expression NN 75 77 of of IN 78 81 the the DT 82 90 retinoic retinoic JJ 91 95 acid acid NN 96 105 receptors receptor NNS 105 106 . . . 108 118 OBJECTIVES objectives NNS 118 119 : : : 120 122 To to TO 123 130 analyze analyze VB 131 134 the the DT 135 141 effect effect NN 142 144 of of IN 145 153 retinoic retinoic JJ 154 159 acids acid NNS 160 161 ( ( ( 161 163 RA RA NNP 163 164 ) ) ) 165 167 on on IN 168 173 HIV-1 HIV-1 NNP 174 184 expression expression NN 185 188 and and CC 189 198 correlate correlate VB 199 203 this this DT 204 210 effect effect NN 211 215 with with IN 216 226 expression expression NN 227 233 levels level NNS 234 236 of of IN 237 239 RA RA NNP 240 249 receptors receptor NNS 250 251 ( ( ( 251 255 RARs RAR NNP 255 256 ) ) ) 257 259 in in IN 260 270 T-lymphoid t-lymphoid JJ 271 274 and and CC 275 285 monocytoid monocytoid JJ 286 290 cell cell NN 291 296 lines line NNS 296 297 . . . 298 304 DESIGN design NN 305 308 AND and CC 309 316 METHODS methods NNS 316 317 : : : 318 321 The the DT 322 328 effect effect NN 329 331 of of IN 332 341 all-trans all-trans JJ 342 345 and and CC 346 351 9-cis 9-cis JJ 352 354 RA RA NNP 355 357 on on IN 358 363 HIV-1 HIV-1 NNP 364 374 production production NN 375 377 in in IN 378 388 T-lymphoid t-lymphoid JJ 389 390 ( ( ( 390 392 H9 H9 NNP 392 393 , , , 394 397 CEM CEM NNP 397 398 ) ) ) 399 402 and and CC 403 413 monocytoid monocytoid NN 414 415 ( ( ( 415 425 U937,THP-1 u937,thp-1 NN 425 426 ) ) ) 427 431 cell cell NN 432 437 lines line NNS 438 441 was be VBD 442 450 measured measure VBN 451 457 during during IN 458 463 acute acute JJ 464 467 and and CC 468 475 chronic chronic JJ 476 485 infection infection NN 485 486 . . . 487 490 The the DT 491 501 expression expression NN 502 508 levels level NNS 509 511 of of IN 512 517 human human JJ 518 521 RAR rar NN 522 527 alpha alpha NN 528 529 ( ( ( 529 533 hRAR hRAR NNP 534 539 alpha alpha NN 539 540 , , , 541 549 receptor receptor NN 550 553 for for IN 554 563 all-trans all-trans JJ 564 566 RA RA NNP 566 567 ) ) ) 568 571 and and CC 572 575 the the DT 576 581 human human JJ 582 592 retinoid-X retinoid-X NNP 593 601 receptor receptor NN 602 607 alpha alpha NN 608 609 ( ( ( 609 613 hRXR hRXR NNP 614 619 alpha alpha NN 620 628 receptor receptor NN 629 632 for for IN 633 638 9-cis 9-cis JJ 639 641 RA RA NNP 641 642 ) ) ) 643 647 were be VBD 648 658 determined determine VBN 659 661 by by IN 662 670 Northern northern NN 671 675 blot blot NN 676 684 analysis analysis NN 684 685 . . . 686 693 RESULTS results NNS 693 694 : : : 695 699 Both both CC 700 709 all-trans all-trans JJ 710 713 and and CC 714 719 9-cis 9-cis JJ 720 722 RA RA NNP 723 732 inhibited inhibit VBD 733 738 virus virus NN 739 750 replication replication NN 751 753 in in IN 754 759 HIV-1 HIV-1 NNP 760 773 IIIB-infected iiib-infected JJ 774 784 monocytoid monocytoid JJ 785 790 cells cell NNS 790 791 , , , 792 794 in in IN 795 798 the the DT 799 807 presence presence NN 808 811 and and CC 812 819 absence absence NN 820 822 of of IN 823 826 the the DT 827 841 co-stimulatory co-stimulatory JJ 842 847 agent agent NN 848 855 phorbol phorbol NN 856 865 myristate myristate NN 866 873 acetate acetate NN 874 875 ( ( ( 875 878 PMA PMA NNP 878 879 ) ) ) 879 880 . . . 881 884 The the DT 885 894 retinoids retinoid NNS 895 898 had have VBD 899 903 weak weak JJ 904 906 or or CC 907 909 no no DT 910 921 stimulatory stimulatory JJ 922 929 effects effect NNS 930 932 on on IN 933 936 HIV HIV NNP 937 947 production production NN 948 950 by by IN 951 957 T-cell t-cell NN 958 963 lines line NNS 963 964 . . . 965 968 HIV HIV NNP 969 979 production production NN 980 982 by by IN 983 997 PMA-stimulated pma-stimulated JJ 998 1004 T-cell t-cell NN 1005 1010 lines line NNS 1011 1014 was be VBD 1015 1024 inhibited inhibit VBN 1025 1027 by by IN 1028 1033 these these DT 1034 1043 retinoids retinoid NNS 1043 1044 . . . 1045 1048 The the DT 1049 1054 9-cis 9-cis JJ 1055 1057 RA RA NNP 1058 1061 was be VBD 1062 1071 generally generally RB 1072 1076 more more RBR 1077 1086 effective effective JJ 1087 1091 than than IN 1092 1101 all-trans all-trans JJ 1102 1104 RA RA NNP 1105 1107 in in IN 1108 1118 inhibiting inhibit VBG 1119 1122 HIV HIV NNP 1123 1133 production production NN 1134 1137 and and CC 1138 1140 in in IN 1141 1152 combination combination NN 1153 1162 generally generally RB 1163 1167 more more RBR 1168 1177 effective effective JJ 1178 1182 than than IN 1183 1186 the the DT 1187 1193 single single JJ 1194 1200 agents agent NNS 1201 1206 alone alone RB 1206 1207 . . . 1208 1213 Human human JJ 1214 1217 RAR RAR NNP 1218 1223 alpha alpha NN 1224 1227 was be VBD 1228 1237 expressed express VBN 1238 1240 in in IN 1241 1243 H9 H9 NNP 1243 1244 , , , 1245 1249 U937 u937 NN 1250 1253 and and CC 1254 1259 THP-1 thp-1 NN 1260 1265 cells cell NNS 1265 1266 , , , 1267 1270 but but CC 1271 1277 almost almost RB 1278 1290 undetectable undetectable JJ 1291 1293 in in IN 1294 1297 CEM CEM NNP 1298 1303 cells cell NNS 1303 1304 . . . 1305 1310 Human human JJ 1311 1314 RXR RXR NNP 1315 1320 alpha alpha NN 1321 1324 was be VBD 1325 1338 significantly significantly RB 1339 1348 expressed express VBN 1349 1351 in in IN 1352 1356 U937 u937 NN 1357 1360 and and CC 1361 1366 THP-1 thp-1 NN 1367 1372 cells cell NNS 1372 1373 , , , 1374 1380 weakly weakly RB 1381 1390 expressed express VBN 1391 1393 in in IN 1394 1396 H9 h9 NN 1397 1402 cells cell NNS 1403 1406 and and CC 1407 1410 not not RB 1411 1421 detectable detectable JJ 1422 1424 in in IN 1425 1428 CEM CEM NNP 1429 1434 cells cell NNS 1434 1435 . . . 1436 1441 After after IN 1442 1453 stimulation stimulation NN 1454 1456 by by IN 1457 1460 PMA PMA NNP 1460 1461 , , , 1462 1465 RXR RXR NNP 1466 1471 alpha alpha NN 1472 1482 expression expression NN 1483 1492 increased increase VBD 1493 1495 in in IN 1496 1498 H9 H9 NNP 1499 1502 and and CC 1503 1507 U937 u937 NN 1508 1513 cells cell NNS 1514 1517 but but CC 1518 1521 not not RB 1522 1524 in in IN 1525 1528 CEM CEM NNP 1529 1534 cells cell NNS 1534 1535 . . . 1536 1541 Human human JJ 1542 1545 RAR RAR NNP 1546 1551 alpha alpha NN 1552 1562 expression expression NN 1563 1566 was be VBD 1567 1576 unchanged unchanged JJ 1577 1579 in in IN 1580 1582 H9 H9 NNP 1583 1586 and and CC 1587 1590 CEM CEM NNP 1591 1596 cells cell NNS 1596 1597 , , , 1598 1601 and and CC 1602 1610 elevated elevate VBN 1611 1613 in in IN 1614 1618 U937 u937 NN 1619 1624 cells cell NNS 1624 1625 , , , 1626 1631 after after IN 1632 1635 PMA PMA NNP 1636 1647 stimulation stimulation NN 1647 1648 . . . 1649 1659 CONCLUSION conclusion NN 1659 1660 : : : 1661 1664 The the DT 1665 1671 effect effect NN 1672 1674 of of IN 1675 1677 RA RA NNP 1678 1680 on on IN 1681 1686 HIV-1 HIV-1 NNP 1687 1697 expression expression NN 1698 1701 was be VBD 1702 1721 cell-type-dependent cell-type-dependent JJ 1722 1725 and and CC 1726 1735 partially partially RB 1736 1746 correlated correlate VBN 1747 1751 with with IN 1752 1760 cellular cellular JJ 1761 1771 expression expression NN 1772 1774 of of IN 1775 1779 RARs RAR NNP 1779 1780 . . . 1781 1791 Endogenous endogenous JJ 1792 1794 or or CC 1795 1806 exogenously exogenously RB 1807 1819 administered administer VBN 1820 1822 RA RA NNP 1823 1826 may may MD 1827 1831 have have VB 1832 1833 a a DT 1834 1845 significant significant JJ 1846 1850 role role NN 1851 1853 in in IN 1854 1857 HIV HIV NNP 1858 1868 regulation regulation NN 1868 1869 . . .