0 7 Protein protein NN 8 14 kinase kinase NNP 15 21 C-zeta C-zeta NNP 22 30 mediates mediate VBZ 31 39 NF-kappa NF-kappa NNP 40 41 B B NNP 42 52 activation activation NN 53 55 in in IN 56 61 human human JJ 62 78 immunodeficiency immunodeficiency NN 79 93 virus-infected virus-infected JJ 94 103 monocytes monocyte NNS 103 104 . . . 106 109 The the DT 110 119 molecular molecular JJ 120 130 mechanisms mechanism NNS 131 141 regulating regulate VBG 142 147 human human JJ 148 164 immunodeficiency immunodeficiency NN 165 170 virus virus NN 171 172 ( ( ( 172 175 HIV HIV NNP 175 176 ) ) ) 177 188 persistence persistence NN 189 191 in in IN 192 193 a a DT 194 199 major major JJ 200 204 cell cell NN 205 214 reservoir reservoir NN 215 219 such such JJ 220 222 as as IN 223 226 the the DT 227 237 macrophage macrophage NN 238 244 remain remain VBP 245 252 unknown unknown JJ 252 253 . . . 254 262 NF-kappa NF-kappa NNP 263 264 B B NNP 265 267 is be VBZ 268 269 a a DT 270 283 transcription transcription NN 284 290 factor factor NN 291 299 involved involve VBN 300 302 in in IN 303 306 the the DT 307 317 regulation regulation NN 318 320 of of IN 321 324 the the DT 325 328 HIV HIV NNP 329 333 long long JJ 334 342 terminal terminal JJ 343 349 repeat repeat NN 350 353 and and CC 354 356 is be VBZ 357 368 selectively selectively RB 369 378 activated activate VBN 379 388 following follow VBG 389 392 HIV HIV NNP 393 402 infection infection NN 403 405 of of IN 406 411 human human JJ 412 423 macrophages macrophage NNS 423 424 . . . 425 433 Although although IN 434 440 little little JJ 441 452 information information NN 453 455 as as IN 456 458 to to TO 459 463 what what WP 464 470 signal signal NN 471 483 transduction transduction NN 484 492 pathways pathway NNS 493 500 mediate mediate VBP 501 509 NF-kappa NF-kappa NNP 510 511 B B NNP 512 522 activation activation NN 523 525 in in IN 526 547 monocytes-macrophages monocytes-macrophage NNS 548 550 is be VBZ 551 560 available available JJ 560 561 , , , 562 565 our our PRP$ 566 574 previous previous JJ 575 579 work work NN 580 589 indicated indicate VBD 590 594 that that IN 595 604 classical classical JJ 605 612 protein protein NN 613 619 kinase kinase NNP 620 621 C C NNP 622 623 ( ( ( 623 626 PKC PKC NNP 626 627 ) ) ) 628 638 isoenzymes isoenzyme NNS 639 643 were be VBD 644 647 not not RB 648 656 involved involve VBN 657 659 in in IN 660 663 the the DT 664 676 HIV-mediated hiv-mediated JJ 677 685 NF-kappa NF-kappa NNP 686 687 B B NNP 688 698 activation activation NN 698 699 . . . 700 702 In in IN 703 707 this this DT 708 713 study study NN 713 714 , , , 715 717 we we PRP 718 722 have have VBP 723 730 focused focus VBN 731 733 on on IN 734 742 atypical atypical JJ 743 746 PKC PKC NNP 747 757 isoenzymes isoenzyme NNS 757 758 . . . 759 767 PKC-zeta PKC-zeta NNP 768 775 belongs belong VBZ 776 778 to to TO 779 783 this this DT 784 790 family family NN 791 794 and and CC 795 797 is be VBZ 798 803 known know VBN 804 806 to to TO 807 809 be be VB 810 812 an an DT 813 822 important important JJ 823 827 step step NN 828 830 in in IN 831 839 NF-kappa NF-kappa NNP 840 841 B B NNP 842 852 activation activation NN 853 855 in in IN 856 861 other other JJ 862 866 cell cell NN 867 874 systems system NNS 874 875 . . . 876 890 Immunoblotting immunoblotting NN 891 902 experiments experiment NNS 903 907 with with IN 908 912 U937 u937 NN 913 918 cells cell NNS 919 930 demonstrate demonstrate VBP 931 935 that that IN 936 944 PKC-zeta PKC-zeta NNP 945 947 is be VBZ 948 955 present present JJ 956 958 in in IN 959 964 these these DT 965 970 cells cell NNS 970 971 , , , 972 975 and and CC 976 979 its its PRP$ 980 990 expression expression NN 991 994 can can MD 995 997 be be VB 998 1011 downmodulated downmodulate VBN 1012 1014 by by IN 1015 1024 antisense antisense JJ 1025 1041 oligonucleotides oligonucleotide NNS 1042 1043 ( ( ( 1043 1045 AO AO NNP 1045 1046 ) ) ) 1046 1047 . . . 1048 1051 The the DT 1052 1064 HIV-mediated hiv-mediated JJ 1065 1073 NF-kappa NF-kappa NNP 1074 1075 B B NNP 1076 1086 activation activation NN 1087 1089 is be VBZ 1090 1101 selectively selectively RB 1102 1109 reduced reduce VBN 1110 1112 by by IN 1113 1115 AO AO NNP 1116 1118 to to TO 1119 1127 PKC-zeta PKC-zeta NNP 1127 1128 . . . 1129 1131 In in IN 1132 1140 addition addition NN 1140 1141 , , , 1142 1156 cotransfection cotransfection NN 1157 1159 of of IN 1160 1161 a a DT 1162 1170 negative negative JJ 1171 1179 dominant dominant JJ 1180 1188 molecule molecule NN 1189 1191 of of IN 1192 1200 PKC-zeta PKC-zeta NNP 1201 1202 ( ( ( 1202 1210 PKC-zeta PKC-zeta NNP 1211 1214 mut mut NN 1214 1215 ) ) ) 1216 1220 with with IN 1221 1229 NF-kappa NF-kappa NNP 1230 1241 B-dependent b-dependent JJ 1242 1250 reporter reporter NN 1251 1256 genes gene NNS 1257 1268 selectively selectively RB 1269 1277 inhibits inhibit VBZ 1278 1281 the the DT 1282 1286 HIV- hiv- NN 1287 1290 but but CC 1291 1294 not not RB 1295 1302 phorbol phorbol NN 1303 1312 myristate myristate NN 1313 1321 acetate- acetate- NN 1322 1324 or or CC 1325 1352 lipopolysaccharide-mediated lipopolysaccharide-mediated JJ 1353 1363 activation activation NN 1364 1366 of of IN 1367 1375 NF-kappa NF-kappa NNP 1376 1378 B. B. NNP 1379 1383 That that DT 1384 1392 PKC-zeta PKC-zeta NNP 1393 1395 is be VBZ 1396 1404 specific specific JJ 1405 1407 in in IN 1408 1418 regulating regulate VBG 1419 1427 NF-kappa NF-kappa NNP 1428 1429 B B NNP 1430 1432 is be VBZ 1433 1442 concluded conclude VBN 1443 1447 from from IN 1448 1451 the the DT 1452 1461 inability inability NN 1462 1464 of of IN 1465 1478 PKC-zeta(mut) pkc-zeta(mut) NN 1479 1481 to to TO 1482 1491 interfere interfere VB 1492 1496 with with IN 1497 1500 the the DT 1501 1506 basal basal JJ 1507 1509 or or CC 1510 1517 phorbol phorbol NN 1518 1527 myristate myristate NN 1528 1545 acetate-inducible acetate-inducible JJ 1546 1551 CREB- creb- NN 1552 1554 or or CC 1555 1568 AP1-dependent ap1-dependent JJ 1569 1584 transcriptional transcriptional JJ 1585 1593 activity activity NN 1593 1594 . . . 1595 1601 Lastly lastly RB 1601 1602 , , , 1603 1605 we we PRP 1606 1617 demonstrate demonstrate VBP 1618 1619 a a DT 1620 1629 selective selective JJ 1630 1640 inhibition inhibition NN 1641 1643 of of IN 1644 1647 p24 p24 NN 1648 1658 production production NN 1659 1661 by by IN 1662 1674 HIV-infected hiv-infected JJ 1675 1680 human human JJ 1681 1692 macrophages macrophage NNS 1693 1697 when when WRB 1698 1705 treated treat VBN 1706 1710 with with IN 1711 1713 AO AO NNP 1714 1716 to to TO 1717 1725 PKC-zeta PKC-zeta NNP 1725 1726 . . . 1727 1737 Altogether altogether RB 1737 1738 , , , 1739 1744 these these DT 1745 1752 results result NNS 1753 1760 suggest suggest VBP 1761 1765 that that IN 1766 1774 atypical atypical JJ 1775 1778 PKC PKC NNP 1779 1789 isoenzymes isoenzyme NNS 1789 1790 , , , 1791 1800 including include VBG 1801 1809 PKC-zeta PKC-zeta NNP 1809 1810 , , , 1811 1822 participate participate VBP 1823 1825 in in IN 1826 1829 the the DT 1830 1836 signal signal NN 1837 1849 transduction transduction NN 1850 1858 pathways pathway NNS 1859 1861 by by IN 1862 1867 which which WDT 1868 1871 HIV HIV NNP 1872 1881 infection infection NN 1882 1889 results result VBZ 1890 1892 in in IN 1893 1896 the the DT 1897 1907 activation activation NN 1908 1910 of of IN 1911 1919 NF-kappa NF-kappa NNP 1920 1921 B B NNP 1922 1924 in in IN 1925 1930 human human JJ 1931 1940 monocytic monocytic JJ 1941 1946 cells cell NNS 1947 1950 and and CC 1951 1962 macrophages macrophage NNS 1962 1963 . . .