0 7 Chronic chronic JJ 8 13 human human JJ 14 30 immunodeficiency immunodeficiency NN 31 36 virus virus NN 37 41 type type NN 42 43 1 1 CD 44 53 infection infection NN 54 56 of of IN 57 64 myeloid myeloid JJ 65 70 cells cell NNS 71 79 disrupts disrupt VBZ 80 83 the the DT 84 98 autoregulatory autoregulatory JJ 99 106 control control NN 107 109 of of IN 110 113 the the DT 114 127 NF-kappaB/Rel NF-kappaB/Rel NNP 128 135 pathway pathway NN 136 139 via via IN 140 148 enhanced enhance VBN 149 161 IkappaBalpha IkappaBalpha NNP 162 173 degradation degradation NN 173 174 . . . 176 186 Productive productive JJ 187 192 human human JJ 193 209 immunodeficiency immunodeficiency NN 210 215 virus virus NN 216 220 type type NN 221 222 1 1 CD 223 224 ( ( ( 224 229 HIV-1 HIV-1 NNP 229 230 ) ) ) 231 240 infection infection NN 241 247 causes cause VBZ 248 257 sustained sustained JJ 258 267 NF-kappaB NF-kappaB NNP 268 279 DNA-binding dna-binding JJ 280 288 activity activity NN 289 291 in in IN 292 303 chronically chronically RB 304 312 infected infected JJ 313 322 monocytic monocytic JJ 323 328 cells cell NNS 328 329 . . . 330 331 A a DT 332 338 direct direct JJ 339 347 temporal temporal JJ 348 359 correlation correlation NN 360 366 exists exist VBZ 367 374 between between IN 375 378 HIV HIV NNP 379 388 infection infection NN 389 392 and and CC 393 396 the the DT 397 407 appearance appearance NN 408 410 of of IN 411 420 NF-kappaB NF-kappaB NNP 421 432 DNA-binding dna-binding JJ 433 441 activity activity NN 442 444 in in IN 445 461 myelomonoblastic myelomonoblastic JJ 462 469 PLB-985 plb-985 NN 470 475 cells cell NNS 475 476 . . . 477 479 To to TO 480 487 examine examine VB 488 491 the the DT 492 501 molecular molecular JJ 502 507 basis basis NN 508 510 of of IN 511 523 constitutive constitutive JJ 524 533 NF-kappaB NF-kappaB NNP 534 545 DNA-binding dna-binding JJ 546 554 activity activity NN 555 557 in in IN 558 562 HIV1 hiv1 NN 563 572 -infected -infected JJ 573 578 cells cell NNS 578 579 , , , 580 582 we we PRP 583 591 analyzed analyze VBD 592 595 the the DT 596 611 phosphorylation phosphorylation NN 612 615 and and CC 616 624 turnover turnover NN 625 627 of of IN 628 640 IkappaBalpha IkappaBalpha NNP 641 648 protein protein NN 648 649 , , , 650 653 the the DT 654 662 activity activity NN 663 665 of of IN 666 669 the the DT 670 685 double-stranded double-stranded JJ 686 699 RNA-dependent rna-dependent JJ 700 707 protein protein NN 708 714 kinase kinase NNP 715 716 ( ( ( 716 719 PKR PKR NNP 719 720 ) ) ) 721 724 and and CC 725 728 the the DT 729 742 intracellular intracellular JJ 743 749 levels level NNS 750 752 of of IN 753 762 NF-kappaB NF-kappaB NNP 763 771 subunits subunit NNS 772 774 in in IN 775 778 the the DT 779 786 PLB-985 PLB-985 NNP 787 790 and and CC 791 795 U937 u937 NN 796 803 myeloid myeloid JJ 804 808 cell cell NN 809 815 models model NNS 815 816 . . . 817 822 HIV-1 HIV-1 NNP 823 832 infection infection NN 833 841 resulted result VBD 842 844 in in IN 845 857 constitutive constitutive JJ 857 858 , , , 859 868 low-level low-level JJ 869 879 expression expression NN 880 882 of of IN 883 887 type type NN 888 889 1 1 CD 890 900 interferon interferon NN 901 902 ( ( ( 902 905 IFN IFN NNP 905 906 ) ) ) 907 909 at at IN 910 913 the the DT 914 918 mRNA mrna NN 919 924 level level NN 924 925 . . . 926 938 Constitutive constitutive JJ 939 942 PKR PKR NNP 943 951 activity activity NN 952 955 was be VBD 956 960 also also RB 961 969 detected detect VBN 970 972 in in IN 973 987 HIV-1-infected hiv-1-infected JJ 988 993 cells cell NNS 994 996 as as IN 997 998 a a DT 999 1005 result result NN 1006 1008 of of IN 1009 1018 low-level low-level JJ 1019 1022 IFN IFN NNP 1023 1033 production production NN 1033 1034 , , , 1035 1040 since since IN 1041 1044 the the DT 1045 1053 addition addition NN 1054 1056 of of IN 1057 1076 anti-IFN-alpha/beta anti-ifn-alpha/beta JJ 1077 1085 antibody antibody NN 1086 1088 to to TO 1089 1092 the the DT 1093 1098 cells cell NNS 1099 1108 decreased decrease VBD 1109 1112 PKR pkr NN 1113 1123 expression expression NN 1123 1124 . . . 1125 1136 Furthermore furthermore RB 1136 1137 , , , 1138 1141 the the DT 1142 1150 analysis analysis NN 1151 1153 of of IN 1154 1166 IkappaBalpha IkappaBalpha NNP 1167 1175 turnover turnover NN 1176 1188 demonstrated demonstrate VBD 1189 1191 an an DT 1192 1201 increased increase VBN 1202 1213 degradation degradation NN 1214 1216 of of IN 1217 1229 IkappaBalpha IkappaBalpha NNP 1230 1232 in in IN 1233 1247 HIV-1-infected hiv-1-infected JJ 1248 1253 cells cell NNS 1254 1258 that that WDT 1259 1262 may may MD 1263 1270 account account VB 1271 1274 for for IN 1275 1278 the the DT 1279 1291 constitutive constitutive JJ 1292 1295 DNA dna NN 1296 1303 binding binding NN 1304 1312 activity activity NN 1312 1313 . . . 1314 1315 A a DT 1316 1324 dramatic dramatic JJ 1325 1333 increase increase NN 1334 1336 in in IN 1337 1340 the the DT 1341 1354 intracellular intracellular JJ 1355 1361 levels level NNS 1362 1364 of of IN 1365 1374 NF-kappaB NF-kappaB NNP 1375 1383 subunits subunit NNS 1384 1389 c-Rel c-rel NN 1390 1393 and and CC 1394 1404 NF-kappaB2 nf-kappab2 NN 1405 1409 p100 p100 NN 1410 1413 and and CC 1414 1415 a a DT 1416 1424 moderate moderate JJ 1425 1433 increase increase NN 1434 1436 in in IN 1437 1447 NF-kappaB2 NF-kappaB2 NNP 1448 1451 p52 p52 NN 1452 1455 and and CC 1456 1465 RelA(p65) RelA(p65) NNP 1466 1470 were be VBD 1471 1479 detected detect VBN 1480 1482 in in IN 1483 1497 HIV-1-infected hiv-1-infected JJ 1498 1503 cells cell NNS 1503 1504 , , , 1505 1512 whereas whereas IN 1513 1523 NF-kappaB1 nf-kappab1 NN 1524 1532 p105/p50 p105/p50 NN 1533 1539 levels level NNS 1540 1544 were be VBD 1545 1548 not not RB 1549 1556 altered alter VBN 1557 1565 relative relative JJ 1566 1568 to to TO 1569 1572 the the DT 1573 1579 levels level NNS 1580 1582 in in IN 1583 1593 uninfected uninfected JJ 1594 1599 cells cell NNS 1599 1600 . . . 1601 1603 We we PRP 1604 1611 suggest suggest VBP 1612 1616 that that IN 1617 1622 HIV-1 HIV-1 NNP 1623 1632 infection infection NN 1633 1635 of of IN 1636 1643 myeloid myeloid JJ 1644 1649 cells cell NNS 1650 1657 induces induce VBZ 1658 1661 IFN ifn NN 1662 1672 production production NN 1673 1676 and and CC 1677 1680 PKR pkr NN 1681 1689 activity activity NN 1689 1690 , , , 1691 1696 which which WDT 1697 1699 in in IN 1700 1704 turn turn NN 1705 1715 contribute contribute VBP 1716 1718 to to TO 1719 1727 enhanced enhance VBN 1728 1740 IkappaBalpha IkappaBalpha NNP 1741 1756 phosphorylation phosphorylation NN 1757 1760 and and CC 1761 1771 subsequent subsequent JJ 1772 1783 degradation degradation NN 1783 1784 . . . 1785 1792 Nuclear nuclear JJ 1793 1806 translocation translocation NN 1807 1809 of of IN 1810 1819 NF-kappaB NF-kappaB NNP 1820 1828 subunits subunit NNS 1829 1832 may may MD 1833 1843 ultimately ultimately RB 1844 1852 increase increase VB 1853 1856 the the DT 1857 1870 intracellular intracellular JJ 1871 1875 pool pool NN 1876 1878 of of IN 1879 1901 NF-kappaB/IkappaBalpha NF-kappaB/IkappaBalpha NNP 1902 1904 by by IN 1905 1907 an an DT 1908 1922 autoregulatory autoregulatory JJ 1923 1932 mechanism mechanism NN 1932 1933 . . . 1934 1942 Enhanced enhance VBN 1943 1951 turnover turnover NN 1952 1954 of of IN 1955 1967 IkappaBalpha IkappaBalpha NNP 1968 1971 and and CC 1972 1975 the the DT 1976 1988 accumulation accumulation NN 1989 1991 of of IN 1992 2005 NF-kappaB/Rel NF-kappaB/Rel NNP 2006 2014 proteins protein NNS 2015 2018 may may MD 2019 2029 contribute contribute VB 2030 2032 to to TO 2033 2036 the the DT 2037 2048 chronically chronically RB 2049 2058 activated activate VBN 2059 2064 state state NN 2065 2067 of of IN 2068 2082 HIV-1-infected hiv-1-infected JJ 2083 2088 cells cell NNS 2088 2089 . . .