A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers

Cell Reports

Volumn 23, Issue 2, 2018, Pages 584-595

  Rutten, Lucy ^a   Lai, Yen Ting ^b   Blokland, Sven ^a   Truan, Daphne ^a   Bisschop, Ilona J M ^a   Strokappe, Nika M ^a   Koornneef, Annemart ^a   van Manen, Danielle ^a   Chuang, Gwo Yu ^b   Farney, S Katie ^b   Schuitemaker, Hanneke ^a   Kwong, Peter D ^b   Langedijk, Johannes P M ^a  

^a Janssen Research and Development   (Netherlands)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

chronic; ConC_base; envelope protein; HIV; hybrid sheet; SOSIP; stabilization; transmitted founder; vaccine; X ray structure

Indexed keywords

VIRUS ENVELOPE PROTEIN; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; RECOMBINANT PROTEIN;

ALPHA HELIX; ANTIGENICITY; ARTICLE; BETA SHEET; CONTROLLED STUDY; CRYSTALLOGRAPHY; EMBRYO; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN REFOLDING; PROTEIN STABILITY; VIRUS STRAIN; BIOSYNTHESIS; CHEMICAL PHENOMENA; CHEMISTRY; DIFFERENTIAL SCANNING CALORIMETRY; GENETICS; ISOLATION AND PURIFICATION; METABOLISM; PROTEIN MULTIMERIZATION; SITE DIRECTED MUTAGENESIS; X RAY CRYSTALLOGRAPHY;

CALORIMETRY, DIFFERENTIAL SCANNING; CRYSTALLOGRAPHY, X-RAY; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; HIV ANTIBODIES; HIV-1; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; MUTAGENESIS, SITE-DIRECTED; PROTEIN CONFORMATION, ALPHA-HELICAL; PROTEIN CONFORMATION, BETA-STRAND; PROTEIN MULTIMERIZATION; PROTEIN REFOLDING; PROTEIN STABILITY; RECOMBINANT PROTEINS;

EID: 85045023441     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2018.03.061     Document Type: Article

References (47)

1. Binley, J.M., Sanders, R.W., Clas, B., Schuelke, N., Master, A., Guo, Y., Kajumo, F., Anselma, D.J., Maddon, P.J., Olson, W.C., Moore, J.P., A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J. Virol. 74 (2000), 627–643.
2. Carlson, J.M., Schaefer, M., Monaco, D.C., Batorsky, R., Claiborne, D.T., Prince, J., Deymier, M.J., Ende, Z.S., Klatt, N.R., DeZiel, C.E., et al. HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck. Science, 345, 2014, 1254031.
3. Chuang, G.Y., Geng, H., Pancera, M., Xu, K., Cheng, C., Acharya, P., Chambers, M., Druz, A., Tsybovsky, Y., Wanninger, T.G., et al. Structure-based design of a soluble prefusion-closed HIV-1 Env trimer with reduced CD4 affinity and improved immunogenicity. J. Virol., 91, 2017 e02268-16.
4. de Taeye, S.W., Ozorowski, G., Torrents de la Peña, A., Guttman, M., Julien, J.P., van den Kerkhof, T.L., Burger, J.A., Pritchard, L.K., Pugach, P., Yasmeen, A., et al. Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposure of non-neutralizing epitopes. Cell 163 (2015), 1702–1715.
5. Dey, A.K., David, K.B., Ray, N., Ketas, T.J., Klasse, P.J., Doms, R.W., Moore, J.P., N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus. Virology 372 (2008), 187–200.
6. Dey, B., Svehla, K., Xu, L., Wycuff, D., Zhou, T., Voss, G., Phogat, A., Chakrabarti, B.K., Li, Y., Shaw, G., et al. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site. PLoS Pathog., 5, 2009, e1000445.
7. Eggink, D., Langedijk, J.P., Bonvin, A.M., Deng, Y., Lu, M., Berkhout, B., Sanders, R.W., Detailed mechanistic insights into HIV-1 sensitivity to three generations of fusion inhibitors. J. Biol. Chem. 284 (2009), 26941–26950.
8. Eglen, R.M., Reisine, T., Roby, P., Rouleau, N., Illy, C., Bossé, R., Bielefeld, M., The Use of AlphaScreen Technology in HTS: Current Status. Curr. Chem. Genomics 1 (2008), 2–10.
9. Feng, Y., Tran, K., Bale, S., Kumar, S., Guenaga, J., Wilson, R., de Val, N., Arendt, H., DeStefano, J., Ward, A.B., Wyatt, R.T., Thermostability of well-ordered HIV spikes correlates with the elicitation of autologous tier 2 neutralizing antibodies. PLoS Pathog., 12, 2016, e1005767.
10. Fischer, W., Perkins, S., Theiler, J., Bhattacharya, T., Yusim, K., Funkhouser, R., Kuiken, C., Haynes, B., Letvin, N.L., Walker, B.D., et al. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat. Med. 13 (2007), 100–106.
11. Garces, F., Lee, J.H., de Val, N., de la Pena, A.T., Kong, L., Puchades, C., Hua, Y., Stanfield, R.L., Burton, D.R., Moore, J.P., et al. Affinity maturation of a potent family of HIV antibodies is primarily focused on accommodating or avoiding glycans. Immunity 43 (2015), 1053–1063.
12. Guenaga, J., Dubrovskaya, V., de Val, N., Sharma, S.K., Carrette, B., Ward, A.B., Wyatt, R.T., Structure-guided redesign increases the propensity of HIV Env to generate highly stable soluble trimers. J. Virol. 90 (2015), 2806–2817.
13. Guenaga, J., Garces, F., de Val, N., Stanfield, R.L., Dubrovskaya, V., Higgins, B., Carrette, B., Ward, A.B., Wilson, I.A., Wyatt, R.T., Glycine substitution at helix-to-coil transitions facilitates the structural determination of a stabilized subtype C HIV envelope glycoprotein. Immunity 46 (2017), 792–803.
14. Guttman, M., Garcia, N.K., Cupo, A., Matsui, T., Julien, J.P., Sanders, R.W., Wilson, I.A., Moore, J.P., Lee, K.K., CD4-induced activation in a soluble HIV-1 Env trimer. Structure 22 (2014), 974–984.
15. Guttman, M., Cupo, A., Julien, J.P., Sanders, R.W., Wilson, I.A., Moore, J.P., Lee, K.K., Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env. Nat. Commun., 6, 2015, 6144.
16. Hastie, K.M., Zandonatti, M.A., Kleinfelter, L.M., Heinrich, M.L., Rowland, M.M., Chandran, K., Branco, L.M., Robinson, J.E., Garry, R.F., Saphire, E.O., Structural basis for antibody-mediated neutralization of Lassa virus. Science 356 (2017), 923–928.
17. Joyce, M.G., Georgiev, I.S., Yang, Y., Druz, A., Geng, H., Chuang, G.-Y., Kwon, Y.D., Pancera, M., Rawi, R., Sastry, M., et al. Soluble prefusion-closed DS-SOSIP.664-Env trimers of diverse HIV-1 strains. Cell Rep. 21 (2017), 2992–3002.
18. Julien, J.P., Cupo, A., Sok, D., Stanfield, R.L., Lyumkis, D., Deller, M.C., Klasse, P.J., Burton, D.R., Sanders, R.W., Moore, J.P., et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342 (2013), 1477–1483.
19. Julien, J.P., Lee, J.H., Ozorowski, G., Hua, Y., Torrents de la Peña, A., de Taeye, S.W., Nieusma, T., Cupo, A., Yasmeen, A., Golabek, M., et al. Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens. Proc. Natl. Acad. Sci. USA 112 (2015), 11947–11952.
20. Kesavardhana, S., Varadarajan, R., Stabilizing the native trimer of HIV-1 Env by destabilizing the heterodimeric interface of the gp41 postfusion six-helix bundle. J. Virol. 88 (2014), 9590–9604.
21. Kong, L., He, L., de Val, N., Vora, N., Morris, C.D., Azadnia, P., Sok, D., Zhou, B., Burton, D.R., Ward, A.B., et al. Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability. Nat. Commun., 7, 2016, 12040.
22. Krarup, A., Truan, D., Furmanova-Hollenstein, P., Bogaert, L., Bouchier, P., Bisschop, I.J., Widjojoatmodjo, M.N., Zahn, R., Schuitemaker, H., McLellan, J.S., Langedijk, J.P., A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism. Nat. Commun., 6, 2015, 8143.
23. Kulp, D.W., Steichen, J.M., Pauthner, M., Hu, X., Schiffner, T., Liguori, A., Cottrell, C.A., Havenar-Daughton, C., Ozorowski, G., Georgeson, E., et al. Structure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding. Nat. Commun., 8, 2017, 1655.
24. Kwon, Y.D., Pancera, M., Acharya, P., Georgiev, I.S., Crooks, E.T., Gorman, J., Joyce, M.G., Guttman, M., Ma, X., Narpala, S., et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat. Struct. Mol. Biol. 22 (2015), 522–531.
25. Langedijk, J.P.M. (2017). Human Immunodeficiency Virus Antigens, Vectors, Compositions, and Methods of Use Thereof. US patent 20170165355, filed December 15, 2016, and published June 15, 2017.
26. Leaman, D.P., Zwick, M.B., Increased functional stability and homogeneity of viral envelope spikes through directed evolution. PLoS Pathog., 9, 2013, e1003184.
27. Lee, J.H., Ozorowski, G., Ward, A.B., Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science 351 (2016), 1043–1048.
28. Liu, J., Bartesaghi, A., Borgnia, M.J., Sapiro, G., Subramaniam, S., Molecular architecture of native HIV-1 gp120 trimers. Nature 455 (2008), 109–113.
29. Lyumkis, D., Julien, J.P., de Val, N., Cupo, A., Potter, C.S., Klasse, P.J., Burton, D.R., Sanders, R.W., Moore, J.P., Carragher, B., et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 342 (2013), 1484–1490.
30. Melikyan, G.B., Markosyan, R.M., Hemmati, H., Delmedico, M.K., Lambert, D.M., Cohen, F.S., Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion. J. Cell Biol. 151 (2000), 413–423.
31. Munro, J.B., Gorman, J., Ma, X., Zhou, Z., Arthos, J., Burton, D.R., Koff, W.C., Courter, J.R., Smith, A.B. 3rd, Kwong, P.D., et al. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science 346 (2014), 759–763.
32. Ozorowski, G., Pallesen, J., de Val, N., Lyumkis, D., Cottrell, C.A., Torres, J.L., Copps, J., Stanfield, R.L., Cupo, A., Pugach, P., et al. Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike. Nature 547 (2017), 360–363.
33. Pallesen, J., Wang, N., Corbett, K.S., Wrapp, D., Kirchdoerfer, R.N., Turner, H.L., Cottrell, C.A., Becker, M.M., Wang, L., Shi, W., et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl. Acad. Sci. USA 114 (2017), E7348–E7357.
34. Pancera, M., Majeed, S., Ban, Y.E., Chen, L., Huang, C.C., Kong, L., Kwon, Y.D., Stuckey, J., Zhou, T., Robinson, J.E., et al. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility. Proc. Natl. Acad. Sci. USA 107 (2010), 1166–1171.
35. Pancera, M., Zhou, T., Druz, A., Georgiev, I.S., Soto, C., Gorman, J., Huang, J., Acharya, P., Chuang, G.Y., Ofek, G., et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514 (2014), 455–461.
36. Ringe, R.P., Ozorowski, G., Yasmeen, A., Cupo, A., Cruz Portillo, V.M., Pugach, P., Golabek, M., Rantalainen, K., Holden, L.G., Cottrell, C.A., et al. Improving the expression and purification of soluble, recombinant native-like HIV-1 envelope glycoprotein trimers by targeted sequence changes. J. Virol., 91, 2017 e00264-17.
37. Sanders, R.W., Vesanen, M., Schuelke, N., Master, A., Schiffner, L., Kalyanaraman, R., Paluch, M., Berkhout, B., Maddon, P.J., Olson, W.C., et al. Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J. Virol. 76 (2002), 8875–8889.
38. Sanders, R.W., Derking, R., Cupo, A., Julien, J.P., Yasmeen, A., de Val, N., Kim, H.J., Blattner, C., de la Peña, A.T., Korzun, J., et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog., 9, 2013, e1003618.
39. Sanders, R.W., Wilson, I.A., Moore, J.P., HIV's Achilles’ Heel. Sci. Am. 315 (2016), 50–55.
40. Schymkowitz, J., Borg, J., Stricher, F., Nys, R., Rousseau, F., Serrano, L., The FoldX web server: an online force field. Nucleic Acids Res., 33, 2005 W382-8.
41. Sok, D., van Gils, M.J., Pauthner, M., Julien, J.P., Saye-Francisco, K.L., Hsueh, J., Briney, B., Lee, J.H., Le, K.M., Lee, P.S., et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc. Natl. Acad. Sci. USA 111 (2014), 17624–17629.
42. Steichen, J.M., Kulp, D.W., Tokatlian, T., Escolano, A., Dosenovic, P., Stanfield, R.L., McCoy, L.E., Ozorowski, G., Hu, X., Kalyuzhniy, O., et al. HIV vaccine design to target germline precursors of glycan-dependent broadly neutralizing antibodies. Immunity 45 (2016), 483–496.
43. Stewart-Jones, G.B., Soto, C., Lemmin, T., Chuang, G.Y., Druz, A., Kong, R., Thomas, P.V., Wagh, K., Zhou, T., Behrens, A.J., et al. Trimeric HIV-1-Env structures define glycan shields from clades A, B, and G. Cell 165 (2016), 813–826.
44. Sullivan, J.T., Sulli, C., Nilo, A., Yasmeen, A., Ozorowski, G., Sanders, R.W., Ward, A.B., Klasse, P.J., Moore, J.P., Doranz, B.J., High-throughput protein engineering improves the antigenicity and stability of soluble HIV-1 envelope glycoprotein SOSIP trimers. J. Virol., 91, 2017, 10.1128/JVI.00862-17.
45. Torrents de la Peña, A., Julien, J.P., de Taeye, S.W., Garces, F., Guttman, M., Ozorowski, G., Pritchard, L.K., Behrens, A.J., Go, E.P., Burger, J.A., et al. Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization. Cell Rep. 20 (2017), 1805–1817.
46. Tully, D.C., Ogilvie, C.B., Batorsky, R.E., Bean, D.J., Power, K.A., Ghebremichael, M., Bedard, H.E., Gladden, A.D., Seese, A.M., Amero, M.A., et al. Differences in the selection bottleneck between modes of sexual transmission influence the genetic composition of the HIV-1 founder virus. PLoS Pathog., 12, 2016, e1005619.
47. Wang, H., Cohen, A.A., Galimidi, R.P., Gristick, H.B., Jensen, G.J., Bjorkman, P.J., Cryo-EM structure of a CD4-bound open HIV-1 envelope trimer reveals structural rearrangements of the gp120 V1V2 loop. Proc. Natl. Acad. Sci. USA 113 (2016), E7151–E7158.