0 5 Human human JJ 6 22 immunodeficiency immunodeficiency NN 23 28 virus virus NN 29 33 type type NN 34 35 1 1 CD 36 40 long long JJ 41 49 terminal terminal JJ 50 56 repeat repeat NN 57 69 quasispecies quasispecy NNS 70 76 differ differ VBP 77 79 in in IN 80 85 basal basal JJ 86 99 transcription transcription NN 100 103 and and CC 104 111 nuclear nuclear JJ 112 118 factor factor NN 119 130 recruitment recruitment NN 131 133 in in IN 134 139 human human JJ 140 145 glial glial JJ 146 151 cells cell NNS 152 155 and and CC 156 167 lymphocytes lymphocyte NNS 167 168 . . . 170 173 The the DT 174 184 generation generation NN 185 187 of of IN 188 195 genomic genomic JJ 196 205 diversity diversity NN 206 212 during during IN 213 216 the the DT 217 223 course course NN 224 226 of of IN 227 236 infection infection NN 237 240 has have VBZ 241 244 the the DT 245 254 potential potential NN 255 257 to to TO 258 264 affect affect VB 265 268 all all DT 269 276 aspects aspect NNS 277 279 of of IN 280 285 HIV-1 HIV-1 NNP 286 297 replication replication NN 297 298 , , , 299 308 including include VBG 309 319 expression expression NN 320 322 of of IN 323 326 the the DT 327 335 proviral proviral JJ 336 342 genome genome NN 342 343 . . . 344 346 To to TO 347 351 gain gain VB 352 353 a a DT 354 360 better good JJR 361 374 understanding understanding NN 375 377 of of IN 378 381 the the DT 382 388 impact impact NN 389 391 of of IN 392 396 long long JJ 397 405 terminal terminal JJ 406 412 repeat repeat NN 413 414 ( ( ( 414 417 LTR LTR NNP 417 418 ) ) ) 419 427 sequence sequence NN 428 437 diversity diversity NN 438 440 on on IN 441 453 LTR-directed ltr-directed JJ 454 458 gene gene NN 459 469 expression expression NN 470 472 in in IN 473 478 cells cell NNS 479 481 of of IN 482 485 the the DT 486 493 central central JJ 494 501 nervous nervous JJ 502 508 system system NN 509 510 ( ( ( 510 513 CNS cns NN 513 514 ) ) ) 515 518 and and CC 519 525 immune immune JJ 526 532 system system NN 532 533 , , , 534 536 we we PRP 537 546 amplified amplify VBD 547 550 and and CC 551 557 cloned clone VBN 558 562 LTRs ltr NNS 563 567 from from IN 568 576 proviral proviral JJ 577 580 DNA dna NN 581 583 in in IN 584 598 HIV-1-infected hiv-1-infected JJ 599 609 peripheral peripheral JJ 610 615 blood blood NN 615 616 . . . 617 625 Sequence sequence NN 626 634 analysis analysis NN 635 637 of of IN 638 646 nineteen nineteen CD 647 651 LTRs ltr NNS 652 658 cloned clone VBN 659 663 from from IN 664 665 2 2 CD 666 671 adult adult JJ 672 675 and and CC 676 677 3 3 CD 678 687 pediatric pediatric JJ 688 696 patients patient NNS 697 705 revealed reveal VBD 706 708 an an DT 709 716 average average NN 717 719 of of IN 720 722 33 33 CD 723 733 nucleotide nucleotide NN 734 741 changes change NNS 742 743 ( ( ( 743 747 with with IN 748 755 respect respect NN 756 758 to to TO 759 762 the the DT 763 771 sequence sequence NN 772 774 of of IN 775 778 the the DT 779 782 LAI LAI NNP 783 786 LTR LTR NNP 786 787 ) ) ) 788 794 within within IN 795 798 the the DT 799 805 455-bp 455-bp JJ 806 808 U3 u3 NN 809 815 region region NN 815 816 . . . 817 826 Transient transient JJ 827 837 expression expression NN 838 846 analyses analysis NNS 847 849 in in IN 850 855 cells cell NNS 856 858 of of IN 859 869 neuroglial neuroglial JJ 870 873 and and CC 874 885 lymphocytic lymphocytic JJ 886 892 origin origin NN 893 905 demonstrated demonstrate VBD 906 910 that that IN 911 915 some some DT 916 918 of of IN 919 924 these these DT 925 929 LTRs LTR NNPS 930 933 had have VBD 934 944 activities activity NNS 945 950 which which WDT 951 957 varied vary VBD 958 971 significantly significantly RB 972 976 from from IN 977 980 the the DT 981 984 LAI LAI NNP 985 988 LTR LTR NNP 989 991 in in IN 992 997 U-373 U-373 NNP 998 1000 MG MG NNP 1001 1006 cells cell NNS 1007 1008 ( ( ( 1008 1010 an an DT 1011 1022 astrocytoma astrocytoma NN 1023 1027 cell cell NN 1028 1032 line line NN 1032 1033 ) ) ) 1034 1036 as as RB 1037 1041 well well RB 1042 1044 as as IN 1045 1047 in in IN 1048 1054 Jurkat Jurkat NNP 1055 1060 cells cell NNS 1061 1062 ( ( ( 1062 1063 a a DT 1064 1076 CD4-positive cd4-positive JJ 1077 1087 lymphocyte lymphocyte NN 1088 1092 cell cell NN 1093 1097 line line NN 1097 1098 ) ) ) 1098 1099 . . . 1100 1105 While while IN 1106 1110 LTRs LTR NNP 1111 1116 which which WDT 1117 1129 demonstrated demonstrate VBD 1130 1133 the the DT 1134 1141 highest high JJS 1142 1152 activities activity NNS 1153 1155 in in IN 1156 1161 U-373 U-373 NNP 1162 1164 MG MG NNP 1165 1170 cells cell NNS 1171 1175 also also RB 1176 1183 yielded yield VBD 1184 1188 high high JJ 1189 1199 activities activity NNS 1200 1202 in in IN 1203 1209 Jurkat Jurkat NNP 1210 1215 cells cell NNS 1215 1216 , , , 1217 1220 the the DT 1221 1225 LTRs ltr NNS 1226 1230 were be VBD 1231 1240 generally generally RB 1241 1245 more more RBR 1246 1252 active active JJ 1253 1255 in in IN 1256 1262 Jurkat Jurkat NNP 1263 1268 cells cell NNS 1269 1273 when when WRB 1274 1282 compared compare VBN 1283 1285 to to TO 1286 1289 the the DT 1290 1293 LAI LAI NNP 1294 1297 LTR LTR NNP 1297 1298 . . . 1299 1310 Differences difference NNS 1311 1313 in in IN 1314 1317 LTR LTR NNP 1318 1326 sequence sequence NN 1327 1331 also also RB 1332 1340 resulted result VBD 1341 1343 in in IN 1344 1355 differences difference NNS 1356 1358 in in IN 1359 1372 transcription transcription NN 1373 1379 factor factor NN 1380 1391 recruitment recruitment NN 1392 1394 to to TO 1395 1405 cis-acting cis-acting JJ 1406 1411 sites site NNS 1412 1418 within within IN 1419 1422 the the DT 1423 1425 U3 u3 NN 1426 1432 region region NN 1433 1435 of of IN 1436 1439 the the DT 1440 1443 LTR ltr NN 1443 1444 , , , 1445 1447 as as IN 1448 1460 demonstrated demonstrate VBN 1461 1463 by by IN 1464 1479 electrophoretic electrophoretic JJ 1480 1488 mobility mobility NN 1489 1494 shift shift NN 1495 1501 assays assay NNS 1501 1502 . . . 1503 1505 In in IN 1506 1516 particular particular JJ 1516 1517 , , , 1518 1527 naturally naturally RB 1528 1537 occurring occur VBG 1538 1546 sequence sequence NN 1547 1556 variation variation NN 1557 1565 impacted impact VBD 1566 1579 transcription transcription NN 1580 1586 factor factor NN 1587 1594 binding bind VBG 1595 1597 to to TO 1598 1600 an an DT 1601 1611 activating activate VBG 1612 1625 transcription transcription NN 1626 1637 factor/cAMP factor/camp NN 1638 1646 response response NN 1647 1654 element element NN 1655 1662 binding binding NN 1663 1664 ( ( ( 1664 1672 ATF/CREB ATF/CREB NNP 1672 1673 ) ) ) 1674 1681 binding binding NN 1682 1686 site site NN 1687 1688 ( ( ( 1688 1695 located located JJ 1696 1703 between between IN 1704 1707 the the DT 1708 1713 LEF-1 lef-1 NN 1714 1717 and and CC 1718 1724 distal distal JJ 1725 1734 NF-kappaB NF-kappaB NNP 1735 1748 transcription transcription NN 1749 1755 factor factor NN 1756 1763 binding binding NN 1764 1769 sites site NNS 1769 1770 ) ) ) 1771 1775 that that WDT 1776 1778 we we PRP 1779 1789 identified identify VBD 1790 1792 in in IN 1793 1801 previous previous JJ 1802 1809 studies study NNS 1810 1812 of of IN 1813 1816 the the DT 1817 1822 HIV-1 HIV-1 NNP 1823 1826 LTR LTR NNP 1826 1827 . . . 1828 1833 These these DT 1834 1842 findings finding NNS 1843 1850 suggest suggest VBP 1851 1855 that that IN 1856 1859 LTR LTR NNP 1860 1868 sequence sequence NN 1869 1876 changes change NNS 1877 1880 can can MD 1881 1894 significantly significantly RB 1895 1901 affect affect VB 1902 1907 basal basal JJ 1908 1911 LTR ltr NN 1912 1920 function function NN 1921 1924 and and CC 1925 1938 transcription transcription NN 1939 1945 factor factor NN 1946 1957 recruitment recruitment NN 1957 1958 , , , 1959 1964 which which WDT 1965 1968 may may MD 1968 1969 , , , 1970 1972 in in IN 1973 1977 turn turn NN 1977 1978 , , , 1979 1984 alter alter VBP 1985 1988 the the DT 1989 1995 course course NN 1996 1998 of of IN 1999 2004 viral viral JJ 2005 2016 replication replication NN 2017 2019 in in IN 2020 2025 cells cell NNS 2026 2028 of of IN 2029 2032 CNS cns NN 2033 2036 and and CC 2037 2043 immune immune JJ 2044 2050 system system NN 2051 2057 origin origin NN 2057 2058 . . .