0 5 HIV-1 HIV-1 NNP 6 18 reactivation reactivation NN 19 21 in in IN 22 29 resting rest VBG 30 40 peripheral peripheral JJ 41 46 blood blood NN 47 58 mononuclear mononuclear JJ 59 64 cells cell NNS 65 67 of of IN 68 76 infected infected JJ 77 83 adults adult NNS 84 88 upon upon IN 89 91 in in FW 92 97 vitro vitro FW 98 101 CD4 cd4 NN 102 115 cross-linking cross-linking NN 116 118 by by IN 119 126 ligands ligand NNS 127 129 of of IN 130 133 the the DT 134 143 CDR2-loop cdr2-loop NN 144 146 in in IN 147 160 extracellular extracellular JJ 161 167 domain domain NN 168 169 1 1 CD 169 170 . . . 172 177 HIV-1 HIV-1 NNP 178 185 infects infect VBZ 186 193 resting rest VBG 194 204 peripheral peripheral JJ 205 210 blood blood NN 211 222 mononuclear mononuclear JJ 223 228 cells cell NNS 229 230 ( ( ( 230 235 PBMCs PBMC NNPS 235 236 ) ) ) 237 240 but but CC 241 248 remains remain VBZ 249 257 inactive inactive JJ 258 263 state state NN 264 269 until until IN 270 280 subsequent subsequent JJ 281 285 cell cell NN 286 296 activation activation NN 296 297 . . . 298 300 We we PRP 301 305 have have VBP 306 318 demonstrated demonstrate VBN 319 323 that that IN 324 327 the the DT 328 341 cross-linking cross-linking NN 342 344 of of IN 345 349 cell cell NN 350 357 surface surface NN 358 361 CD4 cd4 NN 362 364 by by IN 365 381 gp120-anti-gp120 gp120-anti-gp120 NN 382 388 immune immune JJ 389 398 complexes complex NNS 399 401 or or CC 402 418 heat-inactivated heat-inactivated JJ 419 424 HIV-1 HIV-1 NNP 425 426 ( ( ( 426 432 iHIV-1 ihiv-1 NN 432 433 ) ) ) 434 436 is be VBZ 437 447 sufficient sufficient JJ 448 450 to to TO 451 458 trigger trigger VB 459 469 activation activation NN 470 477 signals signal NNS 478 485 leading lead VBG 486 488 to to TO 489 494 virus virus NN 495 507 reactivation reactivation NN 508 509 ( ( ( 509 510 9 9 CD 510 511 ) ) ) 511 512 . . . 513 515 In in IN 516 520 this this DT 521 526 study study NN 526 527 , , , 528 530 we we PRP 531 542 demonstrate demonstrate VBP 543 547 that that IN 548 557 NF-kappaB NF-kappaB NNP 558 565 nuclear nuclear JJ 566 579 translocation translocation NN 580 583 and and CC 584 595 stimulation stimulation NN 596 598 of of IN 599 604 virus virus NN 605 615 production production NN 616 618 by by IN 619 625 iHIV-1 ihiv-1 NN 626 630 were be VBD 631 639 strictly strictly RB 640 646 linked link VBN 647 649 to to TO 650 653 the the DT 654 668 concentrations concentration NNS 669 671 of of IN 672 677 viral viral JJ 678 686 proteins protein NNS 687 691 used use VBN 692 694 as as IN 695 704 exogenous exogenous JJ 705 712 stimuli stimulus NNS 712 713 . . . 714 722 Moreover moreover RB 722 723 , , , 724 726 we we PRP 727 734 further further RB 735 747 investigated investigate VBD 748 751 the the DT 752 763 physiologic physiologic JJ 764 773 relevance relevance NN 774 776 of of IN 777 782 these these DT 783 795 observations observation NNS 795 796 . . . 797 801 When when WRB 802 811 submitted submit VBN 812 814 to to TO 815 817 an an DT 818 820 in in FW 821 826 vitro vitro FW 827 830 CD4 cd4 NN 831 844 cross-linking cross-linking NN 845 847 by by IN 848 854 iHIV-1 ihiv-1 NN 854 855 , , , 856 861 PBMCs pbmc NNS 862 866 from from IN 867 881 HIV-1-infected hiv-1-infected JJ 882 890 patients patient NNS 891 895 were be VBD 896 901 found find VBN 902 904 to to TO 905 912 produce produce VB 913 918 virus virus NN 918 919 . . . 920 924 This this DT 925 930 viral viral JJ 931 943 reactivation reactivation NN 944 947 was be VBD 948 958 associated associate VBN 959 963 with with IN 964 973 increased increase VBN 974 983 NF-kappaB NF-kappaB NNP 984 991 nuclear nuclear JJ 992 1005 translocation translocation NN 1006 1008 in in IN 1009 1017 patients patient NNS 1017 1018 ’ ' POS 1019 1024 PBMCs pbmc NNS 1024 1025 . . . 1026 1038 Additionally additionally RB 1038 1039 , , , 1040 1045 virus virus NN 1046 1058 reactivation reactivation NN 1059 1061 in in IN 1062 1069 resting rest VBG 1070 1075 PBMCs pbmc NNS 1076 1084 infected infect VBN 1085 1087 in in FW 1088 1093 vitro vitro FW 1094 1098 with with IN 1099 1104 HIV-1 HIV-1 NNP 1105 1108 was be VBD 1109 1114 found find VBN 1115 1117 to to TO 1118 1120 be be VB 1121 1133 specifically specifically RB 1134 1141 induced induce VBN 1142 1144 by by IN 1145 1152 ligands ligand NNS 1153 1155 of of IN 1156 1159 the the DT 1160 1169 CDR2-loop cdr2-loop NN 1170 1172 in in IN 1173 1179 domain domain NN 1180 1181 1 1 CD 1182 1183 ( ( ( 1183 1185 D1 d1 NN 1185 1186 ) ) ) 1187 1189 of of IN 1190 1193 CD4 CD4 NNP 1194 1195 ( ( ( 1195 1200 virus virus NN 1201 1209 envelope envelope NN 1210 1213 and and CC 1214 1222 anti-CD4 anti-cd4 JJ 1223 1233 monoclonal monoclonal JJ 1234 1244 antibodies antibody NNS 1244 1245 ) ) ) 1245 1246 . . . 1247 1249 In in IN 1250 1258 contrast contrast NN 1258 1259 , , , 1260 1265 virus virus NN 1266 1278 reactivation reactivation NN 1279 1282 was be VBD 1283 1286 not not RB 1287 1295 observed observe VBN 1296 1305 following follow VBG 1306 1309 CD4 cd4 NN 1310 1325 oligomerization oligomerization NN 1326 1328 by by IN 1329 1339 antibodies antibody NNS 1340 1344 that that WDT 1345 1349 bind bind VBP 1350 1355 other other JJ 1356 1364 epitopes epitope NNS 1365 1367 in in IN 1368 1370 D1 D1 NNP 1370 1371 , , , 1372 1381 including include VBG 1382 1385 the the DT 1386 1398 D1/CDR3-loop d1/cdr3-loop NN 1398 1399 . . . 1400 1407 Finally finally RB 1407 1408 , , , 1409 1416 soluble soluble JJ 1417 1420 CD4 cd4 NN 1421 1422 ( ( ( 1422 1426 sCD4 scd4 NN 1426 1427 ) ) ) 1428 1437 prevented prevent VBD 1438 1443 virus virus NN 1444 1456 reactivation reactivation NN 1457 1459 by by IN 1460 1472 D1/CDR2-loop D1/CDR2-loop NNP 1473 1480 ligands ligand NNS 1480 1481 . . . 1482 1485 Our our PRP$ 1486 1493 results result NNS 1494 1502 indicate indicate VBP 1503 1507 that that IN 1508 1511 the the DT 1512 1521 signaling signaling NN 1522 1528 events event NNS 1529 1538 initiated initiate VBN 1539 1541 in in IN 1542 1547 PBMCs pbmc NNS 1548 1550 by by IN 1551 1566 oligomerization oligomerization NN 1567 1569 of of IN 1570 1573 CD4 cd4 NN 1574 1576 at at IN 1577 1580 the the DT 1581 1593 D1/CDR2-loop D1/CDR2-loop NNP 1594 1597 can can MD 1598 1605 trigger trigger VB 1606 1611 HIV-1 HIV-1 NNP 1612 1624 upregulation upregulation NN 1625 1627 in in IN 1628 1636 infected infected JJ 1637 1648 individuals individual NNS 1648 1649 . . .