0 10 Inhibition Inhibition NNP 11 13 of of IN 14 19 human human JJ 20 36 immunodeficiency immunodeficiency NN 37 42 virus virus NN 43 47 type type NN 48 49 1 1 CD 50 61 replication replication NN 62 64 by by IN 65 66 a a DT 67 80 Tat-activated tat-activated JJ 80 81 , , , 82 92 transduced transduce VBN 93 103 interferon interferon NN 104 108 gene gene NN 108 109 : : : 110 118 targeted target VBN 119 129 expression expression NN 130 132 to to TO 133 138 human human JJ 139 155 immunodeficiency immunodeficiency NN 156 161 virus virus NN 162 166 type type NN 167 177 1-infected 1-infected JJ 178 183 cells cell NNS 183 184 . . . 186 188 We we PRP 189 193 have have VBP 194 202 examined examine VBN 203 206 the the DT 207 218 feasibility feasibility NN 219 221 of of IN 222 227 using use VBG 228 238 interferon interferon NN 239 240 ( ( ( 240 243 IFN IFN NNP 243 244 ) ) ) 245 249 gene gene NN 250 258 transfer transfer NN 259 261 as as IN 262 263 a a DT 264 269 novel novel JJ 270 278 approach approach NN 279 281 to to TO 282 292 anti-human anti-human JJ 293 309 immunodeficiency immunodeficiency NN 310 315 virus virus NN 316 320 type type NN 321 322 1 1 CD 323 324 ( ( ( 324 329 HIV-1 HIV-1 NNP 329 330 ) ) ) 331 338 therapy therapy NN 339 341 in in IN 342 346 this this DT 347 352 study study NN 352 353 . . . 354 356 To to TO 357 362 limit limit VB 363 373 expression expression NN 374 376 of of IN 377 378 a a DT 379 389 transduced transduce VBN 390 395 HIV-1 HIV-1 NNP 396 400 long long JJ 401 409 terminal terminal JJ 410 416 repeat repeat NN 417 418 ( ( ( 418 428 LTR)-IFNA2 LTR)-IFNA2 NNP 429 430 ( ( ( 430 433 the the DT 434 437 new new JJ 438 446 approved approve VBN 447 459 nomenclature nomenclature NN 460 463 for for IN 464 467 IFN IFN NNP 468 473 genes gene NNS 474 476 is be VBZ 477 481 used use VBN 482 492 throughout throughout IN 493 497 this this DT 498 505 article article NN 505 506 ) ) ) 507 513 hybrid hybrid NN 514 518 gene gene NN 519 521 to to TO 522 525 the the DT 526 540 HIV-1-infected hiv-1-infected JJ 541 546 cells cell NNS 546 547 , , , 548 553 HIV-1 HIV-1 NNP 554 557 LTR LTR NNP 558 561 was be VBD 562 570 modified modify VBN 570 571 . . . 572 580 Deletion deletion NN 581 583 of of IN 584 587 the the DT 588 596 NF-kappa NF-kappa NNP 597 598 B B NNP 599 607 elements element NNS 608 610 of of IN 611 614 the the DT 615 620 HIV-1 HIV-1 NNP 621 624 LTR LTR NNP 625 638 significantly significantly RB 639 648 inhibited inhibit VBD 649 661 Tat-mediated tat-mediated JJ 662 677 transactivation transactivation NN 678 680 in in IN 681 687 T-cell t-cell NN 688 693 lines line NNS 693 694 , , , 695 697 as as RB 698 702 well well RB 703 705 as as IN 706 708 in in IN 709 710 a a DT 711 719 monocyte monocyte NN 720 724 line line NN 724 725 , , , 726 730 U937 U937 NNP 730 731 . . . 732 743 Replacement replacement NN 744 746 of of IN 747 750 the the DT 751 759 NF-kappa NF-kappa NNP 760 761 B B NNP 762 770 elements element NNS 771 773 in in IN 774 777 the the DT 778 783 HIV-1 HIV-1 NNP 784 787 LTR LTR NNP 788 790 by by IN 791 792 a a DT 793 796 DNA DNA NNP 797 805 fragment fragment NN 806 813 derived derive VBN 814 818 from from IN 819 822 the the DT 823 834 5’-flanking 5'-flanking JJ 835 841 region region NN 842 844 of of IN 845 859 IFN-stimulated ifn-stimulated JJ 860 864 gene gene NN 865 867 15 15 CD 868 869 ( ( ( 869 874 ISG15 ISG15 NNP 874 875 ) ) ) 875 876 , , , 877 887 containing contain VBG 888 891 the the DT 892 906 IFN-stimulated ifn-stimulated JJ 907 915 response response NN 916 923 element element NN 923 924 , , , 925 934 partially partially RB 935 943 restored restore VBD 944 956 Tat-mediated tat-mediated JJ 957 967 activation activation NN 968 970 of of IN 971 974 LTR LTR NNP 975 977 in in IN 978 979 T t NN 980 985 cells cell NNS 986 988 as as RB 989 993 well well RB 994 996 as as IN 997 999 in in IN 1000 1009 monocytes monocyte NNS 1009 1010 . . . 1011 1020 Insertion Insertion NNP 1021 1023 of of IN 1024 1028 this this DT 1029 1037 chimeric chimeric JJ 1038 1046 promoter promoter NN 1047 1048 ( ( ( 1048 1053 ISG15 ISG15 NNP 1054 1057 LTR LTR NNP 1057 1058 ) ) ) 1059 1067 upstream upstream RB 1068 1070 of of IN 1071 1074 the the DT 1075 1080 human human JJ 1081 1086 IFNA2 ifna2 NN 1087 1091 gene gene NN 1092 1100 directed direct VBD 1101 1105 high high JJ 1106 1112 levels level NNS 1113 1115 of of IN 1116 1119 IFN ifn NN 1120 1129 synthesis synthesis NN 1130 1132 in in IN 1133 1147 Tat-expressing tat-expressing JJ 1148 1153 cells cell NNS 1153 1154 , , , 1155 1160 while while IN 1161 1165 this this DT 1166 1174 promoter promoter NN 1175 1178 was be VBD 1179 1182 not not RB 1183 1193 responsive responsive JJ 1194 1196 to to TO 1197 1202 tumor tumor NN 1203 1211 necrosis necrosis NN 1212 1218 factor factor NN 1219 1233 alpha-mediated alpha-mediated JJ 1234 1244 activation activation NN 1244 1245 . . . 1246 1259 ISG15-LTR-IFN isg15-ltr-ifn NN 1260 1266 hybrid hybrid NN 1267 1271 gene gene NN 1272 1280 inserted insert VBN 1281 1285 into into IN 1286 1289 the the DT 1290 1300 retrovirus retrovirus NN 1301 1307 vector vector NN 1308 1311 was be VBD 1312 1322 transduced transduce VBN 1323 1327 into into IN 1328 1334 Jurkat Jurkat NNP 1335 1338 and and CC 1339 1343 U937 u937 NN 1344 1349 cells cell NNS 1349 1350 . . . 1351 1359 Selected select VBN 1360 1371 transfected transfecte VBN 1372 1378 clones clone NNS 1379 1387 produced produce VBD 1388 1391 low low JJ 1392 1398 levels level NNS 1399 1401 of of IN 1402 1405 IFN IFN NNP 1406 1407 A A NNP 1408 1409 ( ( ( 1409 1413 IFNA IFNA NNP 1413 1414 ) ) ) 1415 1429 constitutively constitutively RB 1429 1430 , , , 1431 1434 and and CC 1435 1440 their their PRP$ 1441 1450 abilities ability NNS 1451 1453 to to TO 1454 1461 express express VB 1462 1475 interleukin-2 interleukin-2 NN 1476 1479 and and CC 1480 1493 interleukin-2 interleukin-2 NN 1494 1502 receptor receptor NN 1503 1507 upon upon IN 1508 1519 stimulation stimulation NN 1520 1524 with with IN 1525 1543 phytohemagglutinin phytohemagglutinin NN 1544 1547 and and CC 1548 1555 phorbol phorbol NN 1556 1565 myristate myristate NN 1566 1573 acetate acetate NN 1574 1578 were be VBD 1579 1587 retained retain VBN 1587 1588 . . . 1589 1600 Enhancement enhancement NN 1601 1603 of of IN 1604 1608 IFNA IFNA NNP 1609 1618 synthesis synthesis NN 1619 1627 observed observe VBN 1628 1632 upon upon IN 1633 1638 HIV-1 HIV-1 NNP 1639 1648 infection infection NN 1649 1657 resulted result VBD 1658 1660 in in IN 1661 1672 significant significant JJ 1673 1683 inhibition inhibition NN 1684 1686 of of IN 1687 1692 HIV-1 HIV-1 NNP 1693 1704 replication replication NN 1705 1708 for for IN 1709 1710 a a DT 1711 1717 period period NN 1718 1720 of of IN 1721 1723 at at IN 1724 1729 least least JJS 1730 1732 30 30 CD 1733 1737 days day NNS 1737 1738 . . . 1739 1744 Virus virus NN 1745 1753 isolated isolate VBN 1754 1758 from from IN 1759 1773 IFNA-producing ifna-producing JJ 1774 1779 cells cell NNS 1780 1783 was be VBD 1784 1788 able able JJ 1789 1791 to to TO 1792 1801 replicate replicate VB 1802 1804 in in IN 1805 1808 the the DT 1809 1813 U937 u937 NN 1814 1819 cells cell NNS 1820 1823 but but CC 1824 1827 did do VBD 1828 1831 not not RB 1832 1841 replicate replicate VB 1842 1853 efficiently efficiently RB 1854 1856 in in IN 1857 1861 U937 u937 NN 1862 1867 cells cell NNS 1868 1878 transduced transduce VBN 1879 1883 with with IN 1884 1887 the the DT 1888 1892 IFNA IFNA NNP 1893 1897 gene gene NN 1897 1898 . . . 1899 1904 These these DT 1905 1912 results result NNS 1913 1920 suggest suggest VBP 1921 1925 that that IN 1926 1935 targeting target VBG 1936 1939 IFN ifn NN 1940 1949 synthesis synthesis NN 1950 1952 to to TO 1953 1967 HIV-1-infected hiv-1-infected JJ 1968 1973 cells cell NNS 1974 1976 is be VBZ 1977 1979 an an DT 1980 1990 attainable attainable JJ 1991 1995 goal goal NN 1996 1999 and and CC 2000 2004 that that IN 2005 2014 autocrine autocrine JJ 2015 2018 IFN IFN NNP 2019 2028 synthesis synthesis NN 2029 2036 results result VBZ 2037 2039 in in IN 2040 2041 a a DT 2042 2054 long-lasting long-lasting JJ 2055 2058 and and CC 2059 2068 permanent permanent JJ 2069 2080 suppression suppression NN 2081 2083 of of IN 2084 2089 HIV-1 HIV-1 NNP 2090 2101 replication replication NN 2101 2102 . . .