0 9 Permanent permanent JJ 10 19 occupancy occupancy NN 20 22 of of IN 23 26 the the DT 27 32 human human JJ 33 49 immunodeficiency immunodeficiency NN 50 55 virus virus NN 56 60 type type NN 61 62 1 1 CD 63 71 enhancer enhancer NN 72 74 by by IN 75 83 NF-kappa NF-kappa NNP 84 85 B B NNP 86 88 is be VBZ 89 95 needed need VBN 96 99 for for IN 100 110 persistent persistent JJ 111 116 viral viral JJ 117 128 replication replication NN 129 131 in in IN 132 141 monocytes monocyte NNS 141 142 . . . 144 148 This this DT 149 153 work work NN 154 159 aimed aim VBN 160 162 to to TO 163 172 ascertain ascertain VB 173 176 the the DT 177 181 role role NN 182 184 of of IN 185 202 kappaB-responsive kappab-responsive JJ 203 211 elements element NNS 212 214 of of IN 215 218 the the DT 219 224 human human JJ 225 241 immunodeficiency immunodeficiency NN 242 247 virus virus NN 248 252 type type NN 253 254 1 1 CD 255 256 ( ( ( 256 261 HIV-1 HIV-1 NNP 261 262 ) ) ) 263 271 enhancer enhancer NN 272 275 not not RB 276 280 only only RB 281 283 in in IN 284 289 early early JJ 290 300 initiation initiation NN 301 304 but but CC 305 309 also also RB 310 312 in in IN 313 322 long-term long-term JJ 323 334 maintenance maintenance NN 335 337 of of IN 338 346 proviral proviral JJ 347 360 transcription transcription NN 361 363 in in IN 364 369 cells cell NNS 370 372 of of IN 373 376 the the DT 377 386 monocytic monocytic JJ 387 394 lineage lineage NN 394 395 . . . 396 399 For for IN 400 404 this this DT 405 412 purpose purpose NN 412 413 , , , 414 416 we we PRP 417 421 used use VBD 422 427 three three CD 428 432 main main JJ 433 443 approaches approach NNS 443 444 . . . 445 448 The the DT 449 454 first first JJ 455 458 was be VBD 459 461 to to TO 462 470 abruptly abruptly RB 471 480 terminate terminate VB 481 486 tumor tumor NN 487 495 necrosis necrosis NN 496 510 factor-induced factor-induced JJ 511 520 NF-kappaB NF-kappaB NNP 521 528 binding bind VBG 529 531 to to TO 532 535 the the DT 536 544 enhancer enhancer NN 545 554 sequences sequence NNS 555 557 in in IN 558 560 U1 u1 NN 561 570 monocytic monocytic JJ 571 576 cells cell NNS 576 577 , , , 578 583 using use VBG 584 585 a a DT 586 591 short short JJ 592 597 pulse pulse NN 598 600 of of IN 601 610 exogenous exogenous JJ 611 616 tumor tumor NN 617 625 necrosis necrosis NN 626 632 factor factor NN 632 633 . . . 634 638 This this DT 639 647 resulted result VBD 648 650 in in IN 651 662 concomitant concomitant JJ 663 671 decrease decrease NN 672 674 in in IN 675 682 nuclear nuclear JJ 683 692 NF-kappaB NF-kappaB NNP 693 704 DNA-binding dna-binding JJ 705 713 activity activity NN 714 717 and and CC 718 728 endogenous endogenous JJ 729 733 long long JJ 734 742 terminal terminal JJ 743 749 repeat repeat NN 750 765 transcriptional transcriptional JJ 766 774 activity activity NN 774 775 . . . 776 779 The the DT 780 786 second second NN 787 790 was be VBD 791 793 to to TO 794 802 suppress suppress VB 803 806 the the DT 807 816 permanent permanent JJ 817 826 NF-kappaB NF-kappaB NNP 827 840 translocation translocation NN 841 848 induced induce VBN 849 851 by by IN 852 857 HIV-1 HIV-1 NNP 858 869 replication replication NN 870 876 itself itself PRP 877 879 in in IN 880 891 chronically chronically RB 892 900 infected infected JJ 901 905 U937 u937 NN 906 911 cells cell NNS 911 912 , , , 913 918 using use VBG 919 920 a a DT 921 929 specific specific JJ 930 940 proteasome proteasome NN 941 950 inhibitor inhibitor NN 951 952 ( ( ( 952 959 Z-LLL-H Z-LLL-H NNP 959 960 ) ) ) 960 961 . . . 962 964 As as RB 965 970 early early RB 971 973 as as IN 974 975 2 2 CD 976 977 h h NN 978 983 after after IN 984 992 addition addition NN 993 995 of of IN 996 999 the the DT 1000 1009 inhibitor inhibitor NN 1010 1012 to to TO 1013 1016 the the DT 1017 1024 culture culture NN 1025 1031 medium medium NN 1031 1032 , , , 1033 1038 there there EX 1039 1042 was be VBD 1043 1045 an an DT 1046 1056 inhibition inhibition NN 1057 1059 of of IN 1060 1064 both both CC 1065 1077 constitutive constitutive JJ 1078 1088 activation activation NN 1089 1091 of of IN 1092 1101 NF-kappaB NF-kappaB NNP 1102 1105 and and CC 1106 1111 HIV-1 HIV-1 NNP 1112 1118 genome genome NN 1119 1129 expression expression NN 1129 1130 . . . 1131 1134 The the DT 1135 1140 third third JJ 1141 1149 approach approach NN 1150 1153 was be VBD 1154 1156 to to TO 1157 1164 monitor monitor VB 1165 1168 the the DT 1169 1180 replication replication NN 1181 1191 competence competence NN 1192 1194 in in IN 1195 1199 U937 u937 NN 1200 1205 cells cell NNS 1206 1208 of of IN 1209 1211 an an DT 1212 1222 infectious infectious JJ 1223 1228 HIV-1 HIV-1 NNP 1229 1237 provirus provirus NN 1238 1246 carrying carry VBG 1247 1252 point point NN 1253 1262 mutations mutation NNS 1263 1265 in in IN 1266 1269 the the DT 1270 1287 kappaB-responsive kappab-responsive JJ 1288 1296 elements element NNS 1297 1299 of of IN 1300 1304 both both CC 1305 1309 long long JJ 1310 1318 terminal terminal JJ 1319 1326 repeats repeat NNS 1326 1327 . . . 1328 1336 Compared compare VBN 1337 1341 with with IN 1342 1345 its its PRP$ 1346 1355 wild-type wild-type JJ 1356 1367 counterpart counterpart NN 1367 1368 , , , 1369 1373 this this DT 1374 1381 mutated mutate VBN 1382 1390 provirus provirus NN 1391 1397 showed show VBD 1398 1399 a a DT 1400 1410 profoundly profoundly RB 1411 1420 decreased decrease VBN 1420 1421 , , , 1422 1441 Z-LLL-H-insensitive z-lll-h-insensitive JJ 1442 1457 transcriptional transcriptional JJ 1458 1461 and and CC 1462 1473 replicative replicative JJ 1474 1482 activity activity NN 1483 1485 in in IN 1486 1490 U937 u937 NN 1491 1500 monocytes monocyte NNS 1500 1501 . . . 1502 1510 Together together RB 1510 1511 , , , 1512 1515 our our PRP$ 1516 1523 results result NNS 1524 1532 indicate indicate VBP 1533 1537 that that IN 1538 1547 occupancy occupancy NN 1548 1550 of of IN 1551 1554 the the DT 1555 1560 viral viral JJ 1561 1569 enhancer enhancer NN 1570 1572 by by IN 1573 1582 NF-kappaB NF-kappaB NNP 1583 1584 ( ( ( 1584 1591 p50/p65 p50/p65 NN 1591 1592 ) ) ) 1593 1605 heterodimers heterodimer NNS 1606 1608 is be VBZ 1609 1617 required require VBN 1618 1621 for for IN 1622 1629 ongoing ongoing JJ 1630 1643 transcription transcription NN 1644 1646 of of IN 1647 1657 integrated integrate VBN 1658 1661 HIV HIV NNP 1662 1670 provirus provirus NN 1671 1673 in in IN 1674 1683 monocytes monocyte NNS 1683 1684 , , , 1685 1689 even even RB 1690 1692 in in IN 1693 1698 cells cell NNS 1699 1710 chronically chronically RB 1711 1719 infected infected JJ 1720 1723 and and CC 1724 1735 permanently permanently RB 1736 1745 producing produce VBG 1746 1756 functional functional JJ 1757 1760 HIV HIV NNP 1761 1764 Tat Tat NNP 1765 1772 protein protein NN 1772 1773 . . . 1774 1778 Thus thus RB 1778 1779 , , , 1780 1783 the the DT 1784 1791 ability ability NN 1792 1794 of of IN 1795 1800 HIV-1 HIV-1 NNP 1801 1812 replication replication NN 1813 1815 to to TO 1816 1824 activate activate VB 1825 1834 NF-kappaB NF-kappaB NNP 1835 1837 is be VBZ 1838 1845 crucial crucial JJ 1846 1848 to to TO 1849 1852 the the DT 1853 1860 intense intense JJ 1861 1877 self-perpetuated self-perpetuated JJ 1878 1883 viral viral JJ 1884 1897 transcription transcription NN 1898 1906 observed observe VBN 1907 1909 in in IN 1910 1915 cells cell NNS 1916 1918 of of IN 1919 1922 the the DT 1923 1932 monocytic monocytic JJ 1933 1940 lineage lineage NN 1940 1941 . . .