0 5 HIV-1 HIV-1 NNP 6 9 Nef Nef NNP 10 15 leads lead VBZ 16 18 to to TO 19 29 inhibition inhibition NN 30 32 or or CC 33 43 activation activation NN 44 46 of of IN 47 48 T t NN 49 54 cells cell NNS 55 64 depending depend VBG 65 67 on on IN 68 71 its its PRP$ 72 85 intracellular intracellular JJ 86 98 localization localization NN 98 99 . . . 101 104 Nef Nef NNP 105 107 of of IN 108 115 primate primate JJ 116 128 lentiviruses lentivirus NNS 129 131 is be VBZ 132 140 required require VBN 141 144 for for IN 145 152 viremia viremia NN 153 156 and and CC 157 168 progression progression NN 169 171 to to TO 172 176 AIDS AIDS NNP 177 179 in in IN 180 187 monkeys monkey NNS 187 188 . . . 189 197 Negative negative JJ 197 198 , , , 199 207 positive positive JJ 207 208 , , , 209 212 and and CC 213 215 no no DT 216 223 effects effect NNS 224 226 of of IN 227 230 Nef Nef NNP 231 235 have have VBP 236 240 also also RB 241 245 been be VBN 246 254 reported report VBN 255 257 on on IN 258 263 viral viral JJ 264 275 replication replication NN 276 278 in in IN 279 284 cells cell NNS 284 285 . . . 286 288 To to TO 289 298 reconcile reconcile VB 299 304 these these DT 305 317 observations observation NNS 317 318 , , , 319 321 we we PRP 322 331 expressed express VBD 332 333 a a DT 334 340 hybrid hybrid NN 341 348 CD8-Nef cd8-nef NN 349 356 protein protein NN 357 359 in in IN 360 366 Jurkat Jurkat NNP 367 372 cells cell NNS 372 373 . . . 374 377 Two two CD 378 386 opposite opposite JJ 387 397 phenotypes phenotype NNS 398 402 were be VBD 403 408 found find VBN 408 409 , , , 410 415 which which WDT 416 424 depended depend VBD 425 427 on on IN 428 431 the the DT 432 445 intracellular intracellular JJ 446 458 localization localization NN 459 461 of of IN 462 465 Nef Nef NNP 465 466 . . . 467 476 Expressed express VBN 477 479 in in IN 480 483 the the DT 484 493 cytoplasm cytoplasm NN 494 496 or or CC 497 499 on on IN 500 503 the the DT 504 508 cell cell NN 509 516 surface surface NN 516 517 , , , 518 521 the the DT 522 529 chimera chimera NN 530 539 inhibited inhibit VBD 540 542 or or CC 543 552 activated activate VBD 553 558 early early JJ 559 568 signaling signaling NN 569 575 events event NNS 576 580 from from IN 581 584 the the DT 585 586 T t NN 587 591 cell cell NN 592 599 antigen antigen NN 600 608 receptor receptor NN 608 609 . . . 610 619 Activated activate VBN 620 626 Jurkat Jurkat NNP 627 632 cells cell NNS 633 637 died die VBD 638 640 by by IN 641 650 apoptosis apoptosis NN 650 651 , , , 652 655 and and CC 656 660 only only RB 661 666 cells cell NNS 667 671 with with IN 672 679 mutated mutate VBN 680 683 nef nef NN 684 689 genes gene NNS 690 700 expressing express VBG 701 710 truncated truncate VBN 711 715 Nefs nef NNS 716 724 survived survive VBD 724 725 , , , 726 731 which which WDT 732 740 rendered render VBD 741 744 Nef Nef NNP 745 758 nonfunctional nonfunctional JJ 758 759 . . . 760 765 These these DT 766 775 mutations mutation NNS 776 786 paralleled parallel VBD 787 792 those those DT 793 795 in in IN 796 801 other other JJ 802 807 viral viral JJ 808 815 strains strain NNS 816 824 passaged passage VBN 825 827 in in FW 828 833 vitro vitro FW 833 834 . . . 835 838 Not not RB 839 843 only only RB 844 846 do do VB 847 852 these these DT 853 863 positional positional JJ 864 871 effects effect NNS 872 874 of of IN 875 878 Nef Nef NNP 879 888 reconcile reconcile VBP 889 896 diverse diverse JJ 897 907 phenotypes phenotype NNS 908 910 of of IN 911 914 Nef Nef NNP 915 918 and and CC 919 926 suggest suggest VBP 927 928 a a DT 929 933 role role NN 934 937 for for IN 938 941 its its PRP$ 942 952 N-terminal n-terminal JJ 953 966 myristylation myristylation NN 966 967 , , , 968 971 but but CC 972 976 they they PRP 977 981 also also RB 982 989 explain explain VBP 990 997 effects effect NNS 998 1000 of of IN 1001 1004 Nef Nef NNP 1005 1007 in in IN 1008 1011 HIV HIV NNP 1012 1021 infection infection NN 1022 1025 and and CC 1026 1037 progression progression NN 1038 1040 to to TO 1041 1045 AIDS AIDS NNP 1045 1046 . . .