0 12 Epstein-Barr epstein-barr JJ 13 18 virus virus NN 19 26 nuclear nuclear JJ 27 34 antigen antigen NN 35 36 2 2 CD 37 51 transactivates transactivate VBZ 52 58 latent latent JJ 59 67 membrane membrane NN 68 75 protein protein NN 76 80 LMP1 lmp1 NN 80 81 . . . 83 90 Several several JJ 91 96 lines line NNS 97 99 of of IN 100 108 evidence evidence NN 109 112 are be VBP 113 123 compatible compatible JJ 124 128 with with IN 129 132 the the DT 133 143 hypothesis hypothesis NN 144 148 that that IN 149 161 Epstein-Barr epstein-barr JJ 162 167 virus virus NN 168 169 ( ( ( 169 172 EBV EBV NNP 172 173 ) ) ) 174 181 nuclear nuclear JJ 182 189 antigen antigen NN 190 191 2 2 CD 192 193 ( ( ( 193 199 EBNA-2 ebna-2 NN 199 200 ) ) ) 201 203 or or CC 204 210 leader leader NN 211 218 protein protein NN 219 220 ( ( ( 220 227 EBNA-LP EBNA-LP NNP 227 228 ) ) ) 229 236 affects affect VBZ 237 247 expression expression NN 248 250 of of IN 251 254 the the DT 255 258 EBV EBV NNP 259 265 latent latent JJ 266 275 infection infection NN 276 284 membrane membrane NN 285 292 protein protein NN 293 297 LMP1 lmp1 NN 297 298 . . . 299 301 We we PRP 302 305 now now RB 306 317 demonstrate demonstrate VBP 318 321 the the DT 322 332 following. following. NN 333 334 ( ( ( 334 335 i i NNP 335 336 ) ) ) 337 342 Acute acute JJ 343 355 transfection transfection NN 356 359 and and CC 360 370 expression expression NN 371 373 of of IN 374 380 EBNA-2 ebna-2 NN 381 386 under under IN 387 394 control control NN 395 397 of of IN 398 404 simian simian JJ 405 410 virus virus NN 411 413 40 40 CD 414 416 or or CC 417 424 Moloney Moloney NNP 425 431 murine murine JJ 432 440 leukemia leukemia NN 441 446 virus virus NN 447 456 promoters promoter NNS 457 465 resulted result VBD 466 468 in in IN 469 478 increased increase VBN 479 483 LMP1 lmp1 NN 484 494 expression expression NN 495 497 in in IN 498 513 P3HR-1-infected p3hr-1-infected JJ 514 521 Burkitt Burkitt NNP 521 523 ’s 's POS 524 532 lymphoma lymphoma NN 533 538 cells cell NNS 539 542 and and CC 543 546 the the DT 547 553 P3HR-1 P3HR-1 NNP 554 556 or or CC 557 562 Daudi Daudi NNP 563 567 cell cell NN 568 573 line. line. NN 574 575 ( ( ( 575 577 ii ii NN 577 578 ) ) ) 579 591 Transfection transfection NN 592 595 and and CC 596 606 expression expression NN 607 609 of of IN 610 617 EBNA-LP EBNA-LP NNP 618 623 alone alone RB 624 627 had have VBD 628 630 no no DT 631 637 effect effect NN 638 640 on on IN 641 645 LMP1 lmp1 NN 646 656 expression expression NN 657 660 and and CC 661 664 did do VBD 665 668 not not RB 669 672 act act VB 673 688 synergistically synergistically RB 689 693 with with IN 694 700 EBNA-2 ebna-2 NN 701 703 to to TO 704 710 affect affect VB 711 715 LMP1 lmp1 NN 716 727 expression. expression. NN 728 729 ( ( ( 729 732 iii iii LS 732 733 ) ) ) 734 738 LMP1 lmp1 NN 739 749 expression expression NN 750 752 in in IN 753 758 Daudi Daudi NNP 759 762 and and CC 763 778 P3HR-1-infected p3hr-1-infected JJ 779 784 cells cell NNS 785 788 was be VBD 789 799 controlled control VBN 800 802 at at IN 803 806 the the DT 807 811 mRNA mrna NN 812 817 level level NN 817 818 , , , 819 822 and and CC 823 829 EBNA-2 ebna-2 NN 830 840 expression expression NN 841 843 in in IN 844 849 Daudi Daudi NNP 850 855 cells cell NNS 856 865 increased increase VBD 866 870 LMP1 lmp1 NN 871 876 mRNA. mrna. NN 877 878 ( ( ( 878 880 iv iv NN 880 881 ) ) ) 882 884 No no DT 885 890 other other JJ 891 894 EBV EBV NNP 895 900 genes gene NNS 901 905 were be VBD 906 914 required require VBN 915 918 for for IN 919 925 EBNA-2 ebna-2 NN 926 941 transactivation transactivation NN 942 944 of of IN 945 949 LMP1 lmp1 NN 950 955 since since IN 956 970 cotransfection cotransfection NN 971 973 of of IN 974 985 recombinant recombinant JJ 986 992 EBNA-2 ebna-2 NN 993 1003 expression expression NN 1004 1011 vectors vector NNS 1012 1015 and and CC 1016 1023 genomic genomic JJ 1024 1028 LMP1 lmp1 NN 1029 1032 DNA dna NN 1033 1042 fragments fragment NNS 1043 1051 enhanced enhance VBD 1052 1056 LMP1 lmp1 NN 1057 1067 expression expression NN 1068 1070 in in IN 1071 1074 the the DT 1075 1087 EBV-negative ebv-negative JJ 1088 1098 B-lymphoma B-lymphoma NNP 1099 1103 cell cell NN 1104 1109 lines line NNS 1110 1114 BJAB BJAB NNP 1114 1115 , , , 1116 1123 Louckes Louckes NNP 1123 1124 , , , 1125 1128 and and CC 1129 1134 BL30. BL30. NNP 1135 1136 ( ( ( 1136 1137 v v NNP 1137 1138 ) ) ) 1139 1141 An an DT 1142 1159 EBNA-2-responsive ebna-2-responsive JJ 1160 1167 element element NN 1168 1171 was be VBD 1172 1177 found find VBN 1178 1184 within within IN 1185 1188 the the DT 1189 1193 -512 -512 CD 1194 1196 to to TO 1197 1200 +40 +40 CD 1201 1205 LMP1 lmp1 NN 1206 1209 DNA dna NN 1210 1215 since since IN 1216 1220 this this DT 1221 1224 DNA dna NN 1225 1231 linked link VBN 1232 1234 to to TO 1235 1236 a a DT 1237 1252 chloramphenicol chloramphenicol NN 1253 1270 acetyltransferase acetyltransferase NN 1271 1279 reporter reporter NN 1280 1284 gene gene NN 1285 1288 was be VBD 1289 1303 transactivated transactivate VBN 1304 1306 by by IN 1307 1321 cotransfection cotransfection NN 1322 1326 with with IN 1327 1329 an an DT 1330 1336 EBNA-2 ebna-2 NN 1337 1347 expression expression NN 1348 1355 vector. vector. NN 1356 1357 ( ( ( 1357 1359 vi vi NN 1359 1360 ) ) ) 1361 1364 The the DT 1365 1368 EBV EBV NNP 1369 1373 type type NN 1374 1375 2 2 CD 1376 1382 EBNA-2 ebna-2 NN 1383 1397 transactivated transactivate VBN 1398 1402 LMP1 lmp1 NN 1403 1405 as as RB 1406 1410 well well RB 1411 1413 as as IN 1414 1417 the the DT 1418 1421 EBV EBV NNP 1422 1426 type type NN 1427 1428 1 1 CD 1429 1436 EBNA-2. EBNA-2. NNP 1437 1438 ( ( ( 1438 1441 vii vii NNS 1441 1442 ) ) ) 1443 1446 Two two CD 1447 1456 deletions deletion NNS 1457 1463 within within IN 1464 1467 the the DT 1468 1474 EBNA-2 ebna-2 NN 1475 1479 gene gene NN 1480 1485 which which WDT 1486 1494 rendered render VBD 1495 1498 EBV EBV NNP 1499 1513 transformation transformation NN 1514 1525 incompetent incompetent NN 1526 1529 did do VBD 1530 1533 not not RB 1534 1547 transactivate transactivate VB 1548 1552 LMP1 lmp1 NN 1552 1553 , , , 1554 1561 whereas whereas IN 1562 1563 a a DT 1564 1588 transformation-competent transformation-competent JJ 1589 1595 EBNA-2 ebna-2 NN 1596 1604 deletion deletion NN 1605 1611 mutant mutant NN 1612 1615 did do VBD 1616 1629 transactivate transactivate VB 1630 1634 LMP1 lmp1 NN 1634 1635 . . . 1636 1640 LMP1 LMP1 NNP 1641 1643 is be VBZ 1644 1645 a a DT 1646 1652 potent potent JJ 1653 1661 effector effector NN 1662 1664 of of IN 1665 1677 B-lymphocyte B-lymphocyte NNP 1678 1688 activation activation NN 1689 1692 and and CC 1693 1696 can can MD 1697 1700 act act VB 1701 1716 synergistically synergistically RB 1717 1721 with with IN 1722 1728 EBNA-2 ebna-2 NN 1729 1731 to to TO 1732 1738 induce induce VB 1739 1747 cellular cellular JJ 1748 1752 CD23 cd23 NN 1753 1757 gene gene NN 1758 1768 expression expression NN 1768 1769 . . . 1770 1774 Thus thus RB 1774 1775 , , , 1776 1782 EBNA-2 ebna-2 NN 1783 1798 transactivation transactivation NN 1799 1801 of of IN 1802 1806 LMP1 LMP1 NNP 1807 1816 amplifies amplify VBZ 1817 1820 the the DT 1821 1831 biological biological JJ 1832 1838 impact impact NN 1839 1841 of of IN 1842 1848 EBNA-2 ebna-2 NN 1849 1852 and and CC 1853 1864 underscores underscore VBZ 1865 1868 its its PRP$ 1869 1876 central central JJ 1877 1881 role role NN 1882 1884 in in IN 1885 1896 EBV-induced ebv-induced JJ 1897 1903 growth growth NN 1904 1918 transformation transformation NN 1918 1919 . . .