0 16 Interferon-gamma Interferon-gamma NNP 17 28 potentiates potentiate VBZ 29 32 the the DT 33 42 antiviral antiviral JJ 43 51 activity activity NN 52 55 and and CC 56 59 the the DT 60 70 expression expression NN 71 73 of of IN 74 95 interferon-stimulated interferon-stimulated JJ 96 101 genes gene NNS 102 109 induced induce VBN 110 112 by by IN 113 129 interferon-alpha interferon-alpha NN 130 132 in in IN 133 137 U937 u937 NN 138 143 cells cell NNS 143 144 . . . 146 153 Binding binding NN 154 156 of of IN 157 161 type type NN 162 163 I i CD 164 174 interferon interferon NN 175 176 ( ( ( 176 190 IFN-alpha/beta IFN-alpha/beta NNP 190 191 ) ) ) 192 194 to to TO 195 203 specific specific JJ 204 213 receptors receptor NNS 214 221 results result VBZ 222 224 in in IN 225 228 the the DT 229 234 rapid rapid JJ 235 250 transcriptional transcriptional JJ 251 261 activation activation NN 261 262 , , , 263 274 independent independent JJ 275 277 of of IN 278 285 protein protein NN 286 295 synthesis synthesis NN 295 296 , , , 297 299 of of IN 300 320 IFN-alpha-stimulated ifn-alpha-stimulated JJ 321 326 genes gene NNS 327 328 ( ( ( 328 332 ISGs ISG NNP 332 333 ) ) ) 334 336 in in IN 337 342 human human JJ 343 354 fibroblasts fibroblast NNS 355 358 and and CC 359 363 HeLa HeLa NNP 364 367 and and CC 368 373 Daudi Daudi NNP 374 378 cell cell NN 379 384 lines line NNS 384 385 . . . 386 389 The the DT 390 397 binding binding NN 398 400 of of IN 401 406 ISGF3 ISGF3 NNP 407 408 ( ( ( 408 422 IFN-stimulated ifn-stimulated JJ 423 427 gene gene NN 428 434 factor factor NN 435 436 3 3 CD 436 437 ) ) ) 438 440 to to TO 441 444 the the DT 445 454 conserved conserve VBN 455 469 IFN-stimulated ifn-stimulated JJ 470 478 response response NN 479 486 element element NN 487 488 ( ( ( 488 492 ISRE ISRE NNP 492 493 ) ) ) 494 501 results result VBZ 502 504 in in IN 505 520 transcriptional transcriptional JJ 521 531 activation activation NN 531 532 . . . 533 537 This this DT 538 544 factor factor NN 545 547 is be VBZ 548 556 composed compose VBN 557 559 of of IN 560 561 a a DT 562 573 DNA-binding dna-binding JJ 574 581 protein protein NN 582 583 ( ( ( 583 588 ISGF3 isgf3 NN 589 594 gamma gamma NN 594 595 ) ) ) 595 596 , , , 597 602 which which WDT 603 611 normally normally RB 612 614 is be VBZ 615 622 present present JJ 623 625 in in IN 626 629 the the DT 630 639 cytoplasm cytoplasm NN 639 640 , , , 641 644 and and CC 645 650 other other JJ 651 670 IFN-alpha-activated ifn-alpha-activated JJ 671 679 proteins protein NNS 680 685 which which WDT 686 694 preexist preexist VBP 695 697 as as IN 698 704 latent latent JJ 705 716 cytoplasmic cytoplasmic JJ 717 727 precursors precursor NNS 728 729 ( ( ( 729 734 ISGF3 isgf3 NN 735 740 alpha alpha NN 740 741 ) ) ) 741 742 . . . 743 745 We we PRP 746 750 have have VBP 751 756 found find VBN 757 761 that that IN 762 765 ISG ISG NNP 766 776 expression expression NN 777 779 in in IN 780 783 the the DT 784 793 monocytic monocytic JJ 794 798 U937 u937 NN 799 803 cell cell NN 804 808 line line NN 809 816 differs differ VBZ 817 821 from from IN 822 826 most most JJS 827 831 cell cell NN 832 837 lines line NNS 838 848 previously previously RB 849 857 examined examine VBN 857 858 . . . 859 863 U937 u937 NN 864 869 cells cell NNS 870 877 express express VBP 878 882 both both CC 883 887 type type NN 888 889 I i CD 890 893 and and CC 894 898 type type NN 899 901 II ii CD 902 905 IFN IFN NNP 906 915 receptors receptor NNS 915 916 , , , 917 920 but but CC 921 925 only only RB 926 935 IFN-alpha IFN-alpha NNP 936 938 is be VBZ 939 946 capable capable JJ 947 949 of of IN 950 958 inducing induce VBG 959 968 antiviral antiviral JJ 969 979 protection protection NN 980 982 in in IN 983 988 these these DT 989 994 cells cell NNS 994 995 . . . 996 1008 Pretreatment Pretreatment NNP 1009 1013 with with IN 1014 1023 IFN-gamma IFN-gamma NNP 1024 1035 potentiates potentiate VBZ 1036 1039 the the DT 1040 1057 IFN-alpha-induced ifn-alpha-induced JJ 1058 1068 protection protection NN 1068 1069 , , , 1070 1073 but but CC 1074 1083 IFN-gamma IFN-gamma NNP 1084 1089 alone alone RB 1090 1094 does do VBZ 1095 1098 not not RB 1099 1103 have have VB 1104 1107 any any DT 1108 1117 antiviral antiviral JJ 1118 1126 activity activity NN 1126 1127 . . . 1128 1133 ISG15 ISG15 NNP 1134 1138 mRNA mRNA NNP 1139 1151 accumulation accumulation NN 1152 1154 in in IN 1155 1159 U937 u937 NN 1160 1165 cells cell NNS 1166 1168 is be VBZ 1169 1172 not not RB 1173 1183 detectable detectable JJ 1184 1190 before before IN 1191 1192 6 6 CD 1193 1194 h h NN 1195 1197 of of IN 1198 1207 IFN-alpha IFN-alpha NNP 1208 1217 treatment treatment NN 1217 1218 , , , 1219 1224 peaks peak VBZ 1225 1227 at at IN 1228 1230 24 24 CD 1231 1232 h h NN 1232 1233 , , , 1234 1237 and and CC 1238 1246 requires require VBZ 1247 1254 protein protein NN 1255 1264 synthesis synthesis NN 1264 1265 . . . 1266 1274 Although although IN 1275 1284 IFN-gamma IFN-gamma NNP 1285 1290 alone alone RB 1291 1295 does do VBZ 1296 1299 not not RB 1300 1306 induce induce VB 1307 1310 ISG ISG NNP 1311 1321 expression expression NN 1321 1322 , , , 1323 1332 IFN-gamma IFN-gamma NNP 1333 1345 pretreatment pretreatment NN 1346 1354 markedly markedly RB 1355 1364 increases increase VBZ 1365 1368 and and CC 1369 1376 hastens hasten VBZ 1377 1380 ISG isg NN 1381 1391 expression expression NN 1392 1395 and and CC 1396 1411 transcriptional transcriptional JJ 1412 1421 induction induction NN 1421 1422 . . . 1423 1430 Nuclear nuclear JJ 1431 1439 extracts extract NNS 1440 1447 assayed assay VBN 1448 1451 for for IN 1452 1455 the the DT 1456 1464 presence presence NN 1465 1467 of of IN 1468 1472 ISRE ISRE NNP 1473 1480 binding binding NN 1481 1488 factors factor NNS 1489 1491 by by IN 1492 1507 electrophoretic electrophoretic JJ 1508 1516 mobility mobility NN 1517 1522 shift shift NN 1523 1529 assays assay NNS 1530 1534 show show VBP 1535 1539 that that IN 1540 1545 ISGF3 isgf3 NN 1546 1548 is be VBZ 1549 1556 induced induce VBN 1557 1559 by by IN 1560 1569 IFN-alpha IFN-alpha NNP 1570 1576 within within IN 1577 1578 6 6 CD 1579 1580 h h NN 1581 1585 from from IN 1586 1598 undetectable undetectable JJ 1599 1604 basal basal JJ 1605 1611 levels level NNS 1612 1614 in in IN 1615 1624 untreated untreated JJ 1625 1629 U937 u937 NN 1630 1635 cells cell NNS 1635 1636 . . . 1637 1647 Activation Activation NNP 1648 1650 of of IN 1651 1656 ISGF3 isgf3 NN 1657 1662 alpha alpha NN 1662 1663 , , , 1664 1667 the the DT 1668 1674 latent latent JJ 1675 1684 component component NN 1685 1687 of of IN 1688 1693 ISGF3 ISGF3 NNP 1693 1694 , , , 1695 1701 occurs occur VBZ 1702 1709 rapidly rapidly RB 1709 1710 . . . 1711 1718 However however RB 1718 1719 , , , 1720 1723 the the DT 1724 1732 increase increase NN 1733 1735 in in IN 1736 1741 ISGF3 isgf3 NN 1742 1750 activity activity NN 1751 1761 ultimately ultimately RB 1762 1772 correlates correlate VBZ 1773 1777 with with IN 1778 1781 the the DT 1782 1794 accumulation accumulation NN 1795 1797 of of IN 1798 1803 ISGF3 isgf3 NN 1804 1809 gamma gamma NN 1810 1817 induced induce VBN 1818 1820 by by IN 1821 1830 IFN-alpha IFN-alpha NNP 1831 1833 or or CC 1834 1843 IFN-gamma IFN-gamma NNP 1843 1844 . . . 1845 1846 ( ( ( 1846 1854 ABSTRACT abstract NN 1855 1864 TRUNCATED truncated VBN 1865 1867 AT at IN 1868 1871 250 250 CD 1872 1877 WORDS words NNS 1877 1878 ) ) )