Pharmacologic inhibition of Nedd8 activation enzyme exposes CD4-induced epitopes within Env on cells expressing HIV-1

Journal of Virology

Volumn 90, Issue 5, 2016, Pages 2486-2502

  Tokarev, Andrey ^a   Stoneham, Charlotte ^b   Lewinski, Mary K ^a,b   Mukim, Amey ^b   Deshmukh, Savitha ^b   Vollbrecht, Thomas ^b   Spina, Celsa A ^a,b   Guatelli, John ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; BONE MARROW STROMAL ANTIGEN 2; CD4 ANTIGEN; CULLIN; CULLIN 1; EPITOPE; INTERFERON; NEDD8 ACTIVATING ENZYME; NEDD8 PROTEIN; PEVONEDISTAT; UBIQUITIN PROTEIN LIGASE; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN; NEDD8 PROTEIN, HUMAN; UBIQUITIN;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ARTICLE; CARBOXY TERMINAL SEQUENCE; CD4+ T LYMPHOCYTE; CELL MEMBRANE; CONTROLLED STUDY; DOWN REGULATION; ENZYME INHIBITION; HEK293 CELL LINE; HELA CELL LINE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; MUTATION; NEF GENE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; T LYMPHOCYTE; VIRION; VIRUS GENE; VIRUS GENOME; VIRUS RELEASE; VPU GENE; ANTAGONISTS AND INHIBITORS; CELL CULTURE; DRUG EFFECTS; EPITHELIUM CELL; IMMUNOLOGY; VIROLOGY;

ANTIBODY-DEPENDENT CELL CYTOTOXICITY; CD4-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; EPITHELIAL CELLS; EPITOPES; HIV-1; HUMANS; UBIQUITINS;

EID: 84961166652     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.02736-15     Document Type: Article

References (56)

1. Guy B, Kieny MP, Riviere Y, Le Peuch C, Dott K, Girard M, Montagnier L, Lecocq JP. 1987. HIV F/3' orf encodes a phosphorylated GTPbinding protein resembling an oncogene product. Nature 330:266-269. http://dx.doi.org/10.1038/330266a0.
2. Willey RL, Maldarelli F, Martin MA, Strebel K. 1992. Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol 66:7193-7200.
3. Van Damme N, Goff D, Katsura C, Jorgenson RL, Mitchell R, Johnson MC, Stephens EB, Guatelli J. 2008. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3:245-252. http://dx.doi.org/10.1016/j.chom.2008.03.001.
4. Sauter D, Schindler M, Specht A, Landford WN, Munch J, Kim KA, Votteler J, Schubert U, Bibollet-Ruche F, Keele BF, Takehisa J, Ogando Y, Ochsenbauer C, Kappes JC, Ayouba A, Peeters M, Learn GH, Shaw G, Sharp PM, Bieniasz P, Hahn BH, Hatziioannou T, Kirchhoff F. 2009. Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe 6:409-421. http://dx.doi.org/10.1016/j.chom.2009.10.004.
5. Pham TN, Lukhele S, Hajjar F, Routy JP, Cohen EA. 2014. HIV Nef and Vpu protect HIV-infected CD4+T cells from antibody-mediated cell lysis through down-modulation of CD4 and BST2. Retrovirology 11:15. http://dx.doi.org/10.1186/1742-4690-11-15.
6. Veillette M, Coutu M, Richard J, Batraville LA, Dagher O, Bernard N, Tremblay C, Kaufmann DE, Roger M, Finzi A. 2015. The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibodydependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals. J Virol 89:545-551. http://dx.doi.org/10.1128/JVI.02868-14.
7. Veillette M, Desormeaux A, Medjahed H, Gharsallah NE, Coutu M, Baalwa J, Guan Y, Lewis G, Ferrari G, Hahn BH, Haynes BF, Robinson JE, Kaufmann DE, Bonsignori M, Sodroski J, Finzi A. 2014. Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibodydependent cell-mediated cytotoxicity. J Virol 88:2633-2644. http://dx.doi.org/10.1128/JVI.03230-13.
8. Arias JF, Heyer LN, von Bredow B, Weisgrau KL, Moldt B, Burton DR, Rakasz EG, Evans DT. 2014. Tetherin antagonism by Vpu protects HIVinfected cells from antibody-dependent cell-mediated cytotoxicity. Proc Natl Acad Sci U S A 111:6425-6430. http://dx.doi.org/10.1073/pnas.1321507111.
9. Alvarez RA, Hamlin RE, Monroe A, Moldt B, Hotta MT, Rodriguez Caprio G, Fierer DS, Simon V, Chen BK. 2014. HIV-1 Vpu antagonism of tetherin inhibits antibody-dependent cellular cytotoxic responses by natural killer cells. J Virol 88:6031-6046. http://dx.doi.org/10.1128/JVI.00449-14.
10. Neil SJ, Zang T, Bieniasz PD. 2008. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425-430. http://dx.doi.org/10.1038/nature06553.
11. Ross TM, Oran AE, Cullen BR. 1999. Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein. Curr Biol 9:613-621. http://dx.doi.org/10.1016/S0960-9822(99)80283-8.
12. Sattentau QJ, Moore JP, Vignaux F, Traincard F, Poignard P. 1993. Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding. J Virol 67:7383-7393.
13. Chaudhuri R, Lindwasser OW, Smith WJ, Hurley JH, Bonifacino JS. 2007. Downregulation of CD4 by human immunodeficiency virus type 1 Nef is dependent on clathrin and involves direct interaction of Nef with the AP2 clathrin adaptor. J Virol 81:3877-3890. http://dx.doi.org/10.1128/JVI.02725-06.
14. Margottin F, Bour SP, Durand H, Selig L, Benichou S, Richard V, Thomas D, Strebel K, Benarous R. 1998. A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol Cell 1:565-574. http://dx.doi.org/10.1016/S1097-2765(00)80056-8.
15. Mitchell RS, Katsura C, Skasko MA, Fitzpatrick K, Lau D, Ruiz A, Stephens EB, Margottin-Goguet F, Benarous R, Guatelli JC. 2009. Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog 5:e1000450. http://dx.doi.org/10.1371/journal.ppat.1000450.
16. Douglas JL, Viswanathan K, McCarroll MN, Gustin JK, Fruh K, Moses AV. 2009. Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a (beta)TrCP-dependent mechanism. J Virol 83:7931-7947. http://dx.doi.org/10.1128/JVI.00242-09.
17. Magadan JG, Perez-Victoria FJ, Sougrat R, Ye Y, Strebel K, Bonifacino JS. 2010. Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps. PLoS Pathog 6:e1000869. http://dx.doi.org/10.1371/journal.ppat.1000869.
18. Tervo HM, Homann S, Ambiel I, Fritz JV, Fackler OT, Keppler OT. 2011. beta-TrCP is dispensable for Vpu's ability to overcome the CD317/Tetherin-imposed restriction to HIV-1 release. Retrovirology 8:9. http://dx.doi.org/10.1186/1742-4690-8-9.
19. Kueck T, Neil SJ. 2012. A cytoplasmic tail determinant in HIV-1 Vpu mediates targeting of tetherin for endosomal degradation and counteracts interferon-induced restriction. PLoS Pathog 8:e1002609. http://dx.doi.org/10.1371/journal.ppat.1002609.
20. Janvier K, Pelchen-Matthews A, Renaud JB, Caillet M, Marsh M, Berlioz-Torrent C. 2011. The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PLoS Pathog 7:e1001265. http://dx.doi.org/10.1371/journal.ppat.1001265.
21. Read MA, Brownell JE, Gladysheva TB, Hottelet M, Parent LA, Coggins MB, Pierce JW, Podust VN, Luo RS, Chau V, Palombella VJ. 2000. Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha. Mol Cell Biol 20:2326-2333. http://dx.doi.org/10.1128/MCB.20.7.2326-2333.2000.
22. Gong L, Yeh ET. 1999. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem 274:12036-12042. http://dx.doi.org/10.1074/jbc.274.17.12036.
23. Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S, Cullis CA, Doucette A, Garnsey JJ, Gaulin JL, Gershman RE, Lublinsky AR, McDonald A, Mizutani H, Narayanan U, Olhava EJ, Peluso S, Rezaei M, Sintchak MD, Talreja T, Thomas MP, Traore T, Vyskocil S, Weatherhead GS, Yu J, Zhang J, Dick LR, Claiborne CF, Rolfe M, Bolen JB, Langston SP. 2009. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458: 732-736. http://dx.doi.org/10.1038/nature07884.
24. Swords RT, Erba HP, DeAngelo DJ, Bixby DL, Altman JK, Maris M, Hua Z, Blakemore SJ, Faessel H, Sedarati F, Dezube BJ, Giles FJ, Medeiros BC. 2015. Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study. Br J Haematol 169:534-543. http://dx.doi.org/10.1111/bjh.13323.
25. Lin JJ, Milhollen MA, Smith PG, Narayanan U, Dutta A. 2010. NEDD8-targeting drug MLN4924 elicitsDNArereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells. Cancer Res 70:10310-10320. http://dx.doi.org/10.1158/0008-5472.CAN-10-2062.
26. Milhollen MA, Traore T, Adams-Duffy J, Thomas MP, Berger AJ, Dang L, Dick LR, Garnsey JJ, Koenig E, Langston SP, Manfredi M, Narayanan U, Rolfe M, Staudt LM, Soucy TA, Yu J, Zhang J, Bolen JB, Smith PG. 2010. MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-(kappa)B-dependent lymphoma. Blood 116:1515-1523. http://dx.doi.org/10.1182/blood-2010-03-272567.
27. Stanley DJ, Bartholomeeusen K, Crosby DC, Kim DY, Kwon E, Yen L, Cartozo NC, Li M, Jager S, Mason-Herr J, Hayashi F, Yokoyama S, Krogan NJ, Harris RS, Peterlin BM, Gross JD. 2012. Inhibition of a NEDD8 cascade restores restriction of HIV by APOBEC3G. PLoS Pathog 8:e1003085. http://dx.doi.org/10.1371/journal.ppat.1003085.
28. Nekorchuk MD, Sharifi HJ, Furuya AK, Jellinger R, de Noronha CM. 2013. HIV relies on neddylation for ubiquitin ligase-mediated functions. Retrovirology 10:138. http://dx.doi.org/10.1186/1742-4690-10-138.
29. Wei W, Guo H, Liu X, Zhang H, Qian L, Luo K, Markham RB, Yu XF. 2014. A first-in-class NAE inhibitor, MLN4924, blocks lentiviral infection in myeloid cells by disrupting neddylation-dependent Vpx-mediated SAMHD1 degradation. J Virol 88:745-751. http://dx.doi.org/10.1128/JVI.02568-13.
30. Spina CA, Kwoh TJ, Chowers MY, Guatelli JC, Richman DD. 1994. The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes. J Exp Med 179:115-123. http://dx.doi.org/10.1084/jem.179.1.115.
31. Alpert MD, Heyer LN, Williams DE, Harvey JD, Greenough T, Allhorn M, Evans DT. 2012. A novel assay for antibody-dependent cell-mediated cytotoxicity against HIV-1-or SIV-infected cells reveals incomplete overlap with antibodies measured by neutralization and binding assays. J Virol 86:12039-12052. http://dx.doi.org/10.1128/JVI.01650-12.
32. Lahm HW, Stein S. 1985. Characterization of recombinant human interleukin-2 with micromethods. J Chromatogr 326:357-361. http://dx.doi.org/10.1016/S0021-9673(01)87461-6.
33. Nguyen KL, Llano M, Akari H, Miyagi E, Poeschla EM, Strebel K, Bour S. 2004. Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression. Virology 319:163-175. http://dx.doi.org/10.1016/j.virol.2003.11.021.
34. Craig HM, Pandori MW, Guatelli JC. 1998. Interaction of HIV-1 Nef with the cellular dileucine-based sorting pathway is required for CD4 down-regulation and optimal viral infectivity. Proc Natl Acad Sci U S A 95:11229-11234. http://dx.doi.org/10.1073/pnas.95.19.11229.
35. Greenberg ME, Bronson S, Lock M, Neumann M, Pavlakis GN, Skowronski J. 1997. Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 downregulation. EMBO J 16:6964-6976. http://dx.doi.org/10.1093/emboj/16.23.6964.
36. Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, Rabson A, Martin MA. 1986. Production of acquired immunodeficiency syndromeassociated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 59:284-291.
37. Klimkait T, Strebel K, Hoggan MD, Martin MA, Orenstein JM. 1990. The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol 64:621-629.
38. Chowers MY, Spina CA, Kwoh TJ, Fitch NJ, Richman DD, Guatelli JC. 1994. Optimal infectivity in vitro of human immunodeficiency virus type 1 requires an intact nef gene. J Virol 68:2906-2914.
39. Homann S, Smith D, Little S, Richman D, Guatelli J. 2011. Upregulation of BST-2/Tetherin by HIV infection in vivo. J Virol 85:10659-10668. http://dx.doi.org/10.1128/JVI.05524-11.
40. Lewinski MK, Jafari M, Zhang H, Opella SJ, Guatelli J. 2015. Membrane anchoring by a C-terminal tryptophan enables HIV-1 Vpu to displace bone marrow stromal antigen 2 (BST2) from sites of viral assembly. J Biol Chem 290:10919-10933. http://dx.doi.org/10.1074/jbc.M114.630095.
41. Jin J, Ang XL, Shirogane T, Wade Harper J. 2005. Identification of substrates for F-box proteins. Methods Enzymol 399:287-309. http://dx.doi.org/10.1016/S0076-6879(05)99020-4.
42. Ramirez PW, DePaula-Silva AB, Szaniawski M, Barker E, Bosque A, Planelles V. 2015. HIV-1 Vpu utilizes both cullin-RING ligase (CRL) dependent and independent mechanisms to downmodulate host proteins. Retrovirology 12:65. http://dx.doi.org/10.1186/s12977-015-0192-2.
43. Pickering S, Hue S, Kim EY, Reddy S, Wolinsky SM, Neil SJ. 2014. Preservation of tetherin and CD4 counter-activities in circulating Vpu alleles despite extensive sequence variation within HIV-1 infected individuals. PLoS Pathog 10:e1003895. http://dx.doi.org/10.1371/journal.ppat.1003895.
44. Kueck T, Foster TL, Weinelt J, Sumner JC, Pickering S, Neil SJ. 2015. Serine phosphorylation of HIV-1 Vpu and its binding to tetherin regulates interaction with clathrin adaptors. PLoS Pathog 11:e1005141. http://dx.doi.org/10.1371/journal.ppat.1005141.
45. Wildum S, Schindler M, Munch J, Kirchhoff F. 2006. Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection. J Virol 80:8047-8059. http://dx.doi.org/10.1128/JVI.00252-06.
46. Chen BK, Gandhi RT, Baltimore D. 1996. CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef. J Virol 70:6044-6053.
47. Lau D, Kwan W, Guatelli J. 2011. Role of the endocytic pathway in the counteraction of BST-2 by human lentiviral pathogens. J Virol 85:9834-9846. http://dx.doi.org/10.1128/JVI.02633-10.
48. McNatt MW, Zang T, Bieniasz PD. 2013. Vpu binds directly to tetherin and displaces it from nascent virions. PLoS Pathog 9:e1003299. http://dx.doi.org/10.1371/journal.ppat.1003299.
49. Jafari M, Guatelli J, Lewinski MK. 2014. Activities of transmitted/founder and chronic clade B HIV-1 Vpu and a C-terminal polymorphism specifically affecting virion release. J Virol 88:5062-5078. http://dx.doi.org/10.1128/JVI.03472-13.
50. Hamer DH. 2004. Can HIV be cured? Mechanisms of HIV persistence and strategies to combat it. Curr HIV Res 2:99-111.
51. Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF. 2012. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36:491-501. http://dx.doi.org/10.1016/j.immuni.2012.01.014.
52. Mangeat B, Gers-Huber G, Lehmann M, Zufferey M, Luban J, Piguet V. 2009. HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog 5:e1000574. http://dx.doi.org/10.1371/journal.ppat.1000574.
53. Jia X, Weber E, Tokarev A, Lewinski M, Rizk M, Suarez M, Guatelli J, Xiong Y. 2014. Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1. Elife 3:e02362. http://dx.doi.org/10.7554/eLife.02362.
54. Calarese DA, Scanlan CN, Zwick MB, Deechongkit S, Mimura Y, Kunert R, Zhu P, Wormald MR, Stanfield RL, Roux KH, Kelly JW, Rudd PM, Dwek RA, Katinger H, Burton DR, Wilson IA. 2003. Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 300:2065-2071. http://dx.doi.org/10.1126/science.1083182.
55. Richard J, Veillette M, Brassard N, Iyer SS, Roger M, Martin L, Pazgier M, Schon A, Freire E, Routy JP, Smith AB, III, Park J, Jones DM, Courter JR, Melillo BN, Kaufmann DE, Hahn BH, Permar SR, Haynes BF, Madani N, Sodroski JG, Finzi A. 2015. CD4 mimetics sensitize HIV-1-infected cells to ADCC. Proc Natl Acad Sci U S A 112:E2687-E2694. http://dx.doi.org/10.1073/pnas.1506755112.
56. Majumder B, Venkatachari NJ, O'Leary S, Ayyavoo V. 2008. Infection with Vpr-positive human immunodeficiency virus type 1 impairs NK cell function indirectly through cytokine dysregulation of infected target cells. J Virol 82:7189-7200. http://dx.doi.org/10.1128/JVI.01979-07.