0 15 TAR-independent tar-independent JJ 16 31 transactivation transactivation NN 32 34 by by IN 35 38 Tat Tat NNP 39 41 in in IN 42 47 cells cell NNS 48 55 derived derive VBN 56 60 from from IN 61 64 the the DT 65 68 CNS cns NN 68 69 : : : 70 71 a a DT 72 77 novel novel JJ 78 87 mechanism mechanism NN 88 90 of of IN 91 96 HIV-1 HIV-1 NNP 97 101 gene gene NN 102 112 regulation regulation NN 112 113 . . . 115 118 The the DT 119 122 Tat Tat NNP 123 130 protein protein NN 131 133 of of IN 134 139 human human JJ 140 156 immunodeficiency immunodeficiency NN 157 162 virus virus NN 163 167 type type NN 168 169 1 1 CD 170 171 ( ( ( 171 176 HIV-1 HIV-1 NNP 176 177 ) ) ) 178 180 is be VBZ 181 190 essential essential JJ 191 194 for for IN 195 205 productive productive JJ 206 215 infection infection NN 216 219 and and CC 220 222 is be VBZ 223 224 a a DT 225 234 potential potential JJ 235 241 target target NN 242 245 for for IN 246 255 antiviral antiviral JJ 256 263 therapy therapy NN 263 264 . . . 265 268 Tat Tat NNP 268 269 , , , 270 271 a a DT 272 278 potent potent JJ 279 288 activator activator NN 289 291 of of IN 292 297 HIV-1 HIV-1 NNP 298 302 gene gene NN 303 313 expression expression NN 313 314 , , , 315 321 serves serve VBZ 322 324 to to TO 325 332 greatly greatly RB 333 341 increase increase VB 342 345 the the DT 346 350 rate rate NN 351 353 of of IN 354 367 transcription transcription NN 368 376 directed direct VBN 377 379 by by IN 380 383 the the DT 384 389 viral viral JJ 390 398 promoter promoter NN 398 399 . . . 400 404 This this DT 405 414 induction induction NN 414 415 , , , 416 421 which which WDT 422 427 seems seem VBZ 428 430 to to TO 431 433 be be VB 434 436 an an DT 437 446 important important JJ 447 456 component component NN 457 459 in in IN 460 463 the the DT 464 475 progression progression NN 476 478 of of IN 479 487 acquired acquire VBN 488 494 immune immune JJ 495 505 deficiency deficiency NN 506 514 syndrome syndrome NN 515 516 ( ( ( 516 520 AIDS AIDS NNP 520 521 ) ) ) 521 522 , , , 523 526 may may MD 527 529 be be VB 530 533 due due JJ 534 536 to to TO 537 546 increased increase VBN 547 562 transcriptional transcriptional JJ 563 573 initiation initiation NN 573 574 , , , 575 584 increased increase VBN 585 600 transcriptional transcriptional JJ 601 611 elongation elongation NN 611 612 , , , 613 615 or or CC 616 617 a a DT 618 629 combination combination NN 630 632 of of IN 633 638 these these DT 639 648 processes process NNS 648 649 . . . 650 654 Much much JJ 655 664 attention attention NN 665 668 has have VBZ 669 673 been be VBN 674 681 focused focus VBN 682 684 on on IN 685 688 the the DT 689 700 interaction interaction NN 701 703 of of IN 704 707 Tat Tat NNP 708 712 with with IN 713 714 a a DT 715 723 specific specific JJ 724 727 RNA RNA NNP 728 734 target target NN 735 741 termed term VBN 742 745 TAR TAR NNP 746 747 ( ( ( 747 762 transactivation transactivation NN 763 773 responsive responsive JJ 773 774 ) ) ) 775 780 which which WDT 781 783 is be VBZ 784 791 present present JJ 792 794 in in IN 795 798 the the DT 799 805 leader leader NN 806 814 sequence sequence NN 815 817 of of IN 818 821 all all DT 822 827 HIV-1 HIV-1 NNP 828 833 mRNAs mrna NNS 833 834 . . . 835 839 This this DT 840 851 interaction interaction NN 852 854 is be VBZ 855 863 believed believe VBN 864 866 to to TO 867 869 be be VB 870 872 an an DT 873 882 important important JJ 883 892 component component NN 893 895 of of IN 896 899 the the DT 900 909 mechanism mechanism NN 910 912 of of IN 913 928 transactivation transactivation NN 928 929 . . . 930 932 In in IN 933 937 this this DT 938 944 report report NN 945 947 we we PRP 948 959 demonstrate demonstrate VBP 960 964 that that IN 965 967 in in IN 968 975 certain certain JJ 976 987 CNS-derived cns-derived JJ 988 993 cells cell NNS 994 997 Tat Tat NNP 998 1000 is be VBZ 1001 1008 capable capable JJ 1009 1011 of of IN 1012 1022 activating activate VBG 1023 1028 HIV-1 HIV-1 NNP 1029 1036 through through IN 1037 1038 a a DT 1039 1054 TAR-independent tar-independent JJ 1055 1062 pathway pathway NN 1062 1063 . . . 1064 1065 A a DT 1066 1080 Tat-responsive tat-responsive JJ 1081 1088 element element NN 1089 1091 is be VBZ 1092 1097 found find VBN 1098 1106 upstream upstream RB 1107 1113 within within IN 1114 1117 the the DT 1118 1123 viral viral JJ 1124 1132 promoter promoter NN 1133 1137 that that IN 1138 1140 in in IN 1141 1154 glial-derived glial-derived JJ 1155 1159 cell cell NN 1160 1165 lines line NNS 1166 1172 allows allow VBZ 1173 1188 transactivation transactivation NN 1189 1191 in in IN 1192 1195 the the DT 1196 1203 absence absence NN 1204 1206 of of IN 1207 1210 TAR TAR NNP 1210 1211 . . . 1212 1220 Deletion deletion NN 1221 1228 mapping mapping NN 1229 1232 and and CC 1233 1239 hybrid hybrid NN 1240 1248 promoter promoter NN 1249 1259 constructs construct NNS 1260 1271 demonstrate demonstrate VBP 1272 1276 that that IN 1277 1280 the the DT 1281 1286 newly newly RB 1287 1297 identified identify VBN 1298 1312 Tat-responsive tat-responsive JJ 1313 1320 element element NN 1321 1332 corresponds correspond VBZ 1333 1335 to to TO 1336 1337 a a DT 1338 1346 sequence sequence NN 1347 1353 within within IN 1354 1357 the the DT 1358 1363 viral viral JJ 1364 1368 long long JJ 1369 1377 terminal terminal JJ 1378 1384 repeat repeat NN 1385 1386 ( ( ( 1386 1389 LTR LTR NNP 1389 1390 ) ) ) 1391 1401 previously previously RB 1402 1412 identified identify VBN 1413 1415 as as IN 1416 1419 the the DT 1420 1425 HIV-1 HIV-1 NNP 1426 1434 enhancer enhancer NN 1434 1435 , , , 1436 1438 or or CC 1439 1447 NF-kappa NF-kappa NNP 1448 1449 B B NNP 1450 1456 domain domain NN 1456 1457 . . . 1458 1461 DNA DNA NNP 1462 1472 band-shift band-shift NN 1473 1481 analysis analysis NN 1482 1489 reveals reveal VBZ 1490 1498 NF-kappa NF-kappa NNP 1499 1500 B B NNP 1501 1508 binding binding NN 1509 1517 activity activity NN 1518 1520 in in IN 1521 1526 glial glial JJ 1527 1532 cells cell NNS 1533 1537 that that WDT 1538 1545 differs differ VBZ 1546 1550 from from IN 1551 1555 that that DT 1556 1563 present present JJ 1564 1566 in in IN 1567 1568 T t NN 1569 1577 lymphoid lymphoid JJ 1578 1583 cells cell NNS 1583 1584 . . . 1585 1592 Further further RB 1592 1593 , , , 1594 1596 we we PRP 1597 1604 observe observe VBP 1605 1609 that that IN 1610 1621 TAR-deleted tar-deleted JJ 1622 1629 mutants mutant NNS 1630 1632 of of IN 1633 1638 HIV-1 HIV-1 NNP 1639 1650 demonstrate demonstrate VBP 1651 1657 normal normal JJ 1658 1662 late late JJ 1663 1667 gene gene NN 1668 1678 expression expression NN 1679 1681 in in IN 1682 1687 glial glial JJ 1688 1693 cells cell NNS 1694 1696 as as IN 1697 1706 evidenced evidence VBN 1707 1709 by by IN 1710 1718 syncytia syncytia NN 1719 1728 formation formation NN 1729 1732 and and CC 1733 1743 production production NN 1744 1746 of of IN 1747 1752 viral viral JJ 1753 1756 p24 p24 NN 1757 1764 antigen antigen NN 1764 1765 . . . 1766 1767 ( ( ( 1767 1775 ABSTRACT abstract NN 1776 1785 TRUNCATED truncated VBN 1786 1788 AT at IN 1789 1792 250 250 CD 1793 1798 WORDS words NNS 1798 1799 ) ) )