Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies

Science Translational Medicine

Volumn 9, Issue 373, 2017, Pages

  Petrovas, Constantinos ^a   Ferrando Martinez, Sara ^a   Gerner, Michael Y ^a,i   Casazza, Joseph P ^a   Pegu, Amarendra ^a   Deleage, Claire ^b   Cooper, Arik ^a   Hataye, Jason ^a   Andrews, Sarah ^a   Ambrozak, David ^a   Del Río Estrada, Perla M ^c   Boritz, Eli ^a   Paris, Robert ^d   Moysi, Eirini ^a   Boswell, Kristin L ^a   Ruiz Mateos, Ezequiel ^e   Vagios, Ilias ^f   Leal, Manuel ^e   Ablanedo Terrazas, Yuria ^c   Rivero, Amaranta ^c   Gonzalez Hernandez, Luz Alicia ^c   McDermott, Adrian B ^a   Moir, Susan ^a   Reyes Terán, Gustavo ^c   Docobo, Fernando ^e   Pantaleo, Giuseppe ^g   Douek, Daniel C ^a   Betts, Michael R ^h   Estes, Jacob D ^b   Germain, Ronald N ^a   Mascola, John R ^a   Koup, Richard A ^a   more..

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

^b FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH   (United States)

^c INSTITUTO NACIONAL DE ENFERMEDADES RESPIRATORIAS   (Mexico)

^d WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^e HOSPITAL UNIVERSITARIO VIRGEN DEL ROCÍO   (Spain)

^f Venizelion General Hospital   (Greece)

^g LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^h UNIVERSITY OF PENNSYLVANIA   (United States)

ⁱ UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BISPECIFIC ANTIBODY; CYTOKINE; GRANZYME B; PERFORIN; GRANZYME; GZMB PROTEIN, HUMAN; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY;

ADULT; ARTICLE; CD8+ T LYMPHOCYTE; CELLULAR DISTRIBUTION; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; FOLLICULAR CD8+ T LYMPHOCYTE; GERMINAL CENTER; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HUMAN TISSUE; IMMUNOREACTIVITY; IN VITRO STUDY; LYMPH FOLLICLE; VIRUS REPLICATION; AGED; CYTOLOGY; FEMALE; IMMUNOLOGY; LYMPH NODE; MALE; MIDDLE AGED; PALATINE TONSIL; PHENOTYPE;

ADULT; AGED; ANTIBODIES, BISPECIFIC; CD8-POSITIVE T-LYMPHOCYTES; CYTOKINES; FEMALE; GRANZYMES; HIV ANTIBODIES; HIV INFECTIONS; HUMANS; LYMPH NODES; MALE; MIDDLE AGED; PALATINE TONSIL; PERFORIN; PHENOTYPE;

EID: 85010304642     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aag2285     Document Type: Article

References (59)

1. E. Connick, T. Mattila, J. M. Folkvord, R. Schlichtemeier, A. L. Meditz, M. G. Ray, M. D. McCarter, S. MaWhinney, A. Hage, C. White, P. J. Skinner, CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue. J. Immunol. 178, 6975-6983 (2007).
2. J. Embretson, M. Zupancic, J. L. Ribas, A. Burke, P. Racz, K. Tenner-Racz, A. T. Haase, Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 362, 359-362 (1993).
3. J. M. Folkvord, C. Armon, E. Connick, Lymphoid follicles are sites of heightened human immunodeficiency virus type 1 (HIV-1) replication and reduced antiretroviral effector mechanisms. AIDS Res. Hum. Retroviruses 21, 363-370 (2005).
4. S. Gratton, R. Cheynier, M. J. Dumaurier, E. Oksenhendler, S. Wain-Hobson, Highly restricted spread of HIV-1 and multiply infected cells within splenic germinal centers. Proc. Natl. Acad. Sci. U.S.A. 97, 14566-14571 (2000).
5. F. T. Hufert, J. van Lunzen, G. Janossy, S. Bertram, J. Schmitz, O. Haller, P. Racz, D. von Laer, Germinal centre CD4+ T cells are an important site of HIV replication in vivo. AIDS 11, 849-857 (1997).
6. G. Pantaleo, C. Graziosi, J. F. Demarest, L. Butini, M. Montroni, C. H. Fox, J. M. Orenstein, D. P. Kotler, A. S. Fauci, HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362, 355-358 (1993).
7. M. Lindqvist, J. van Lunzen, D. Z. Soghoian, B. D. Kuhl, S. Ranasinghe, G. Kranias, M. D. Flanders, S. Cutler, N. Yudanin, M. I. Muller, I. Davis, D. Farber, P. Hartjen, F. Haag, G. Alter, J. Schulze zur Wiesch, H. Streeck, Expansion of HIV-specific T follicular helper cells in chronic HIV infection. J. Clin. Invest. 122, 3271-3280 (2012).
8. M. Perreau, A.-L. Savoye, E. De Crignis, J.-M. Corpataux, R. Cubas, E. K. Haddad, L. De Leval, C. Graziosi, G. Pantaleo, Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J. Exp. Med. 210, 143-156 (2013).
9. Y. Xu, C. Weatherall, M. Bailey, S. Alcantara, R. De Rose, J. Estaquier, K. Wilson, K. Suzuki, J. Corbeil, D. A. Cooper, S. J. Kent, A. D. Kelleher, J. Zaunders, Simian immunodeficiency virus infects follicular helper CD4 T cells in lymphoid tissues during pathogenic infection of pigtail macaques. J. Virol. 87, 3760-3773 (2013).
10. Y. Fukazawa, R. Lum, A. A. Okoye, H. Park, K. Matsuda, J. Y. Bae, S. I. Hagen, R. Shoemaker, C. Deleage, C. Lucero, D. Morcock, T. Swanson, A. W. Legasse, M. K. Axthelm, J. Hesselgesser, R. Geleziunas, V. M. Hirsch, P. T. Edlefsen, M. Piatak Jr., J. D. Estes J. D. Lifson, L. J. Picker, B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat. Med. 21, 132-139 (2015).
11. M. F. Quigley, V. D. Gonzalez, A. Granath, J. Andersson, J. K. Sandberg, CXCR5+ CCR7- CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles. Eur. J. Immunol. 37, 3352-3362 (2007).
12. Y. A. Leong, Y. Chen, H. S. Ong, D. Wu, K. Man, C. Deleage, M. Minnich, B. J. Meckiff, Y. Wei, Z. Hou, D. Zotos, K. A. Fenix, A. Atnerkar, S. Preston, J. G. Chipman, G. J. Beilman, C. C. Allison, L. Sun, P. Wang, J. Xu, J. G. Toe, H. K. Lu, Y. Tao, U. Palendira, A. L. Dent, A. L. Landay, M. Pellegrini, I. Comerford, S. R. McColl, T. W. Schacker, H. M. Long, J. D. Estes, M. Busslinger, G. T. Belz, S. R. Lewin, A. Kallies, D. Yu, CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles. Nat. Immunol. 17, 1187-1196 (2016).
13. R. He, S. Hou, C. Liu, A. Zhang, Q. Bai, M. Han, Y. Yang, G. Wei, T. Shen, X. Yang, L. Xu, X. Chen, Y. Hao, P. Wang, C. Zhu, J. Ou, H. Liang, T. Ni, X. Zhang, X. Zhou, K. Deng, Y. Chen, Y. Luo, J. Xu, H. Qi, Y. Wu, L. Ye, Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection. Nature 537, 412-428 (2016).
14. M. Altfeld, J. van Lunzen, N. Frahm, X. G. Yu, C. Schneider, R. L. Eldridge, M. E. Feeney, D. Meyer-Olson, H.-J. Stellbrink, B. D. Walker, Expansion of pre-existing, lymph node-localized CD8+ T cells during supervised treatment interruptions in chronic HIV-1 infection. J. Clin. Invest. 109, 837-843 (2002).
15. K. Ellefsen, A. Harari, P. Champagne, P.-A. Bart, R.-P. Sékaly, G. Pantaleo, Distribution and functional analysis of memory antiviral CD8 T cell responses in HIV-1 and cytomegalovirus infections. Eur. J. Immunol. 32, 3756-3764 (2002).
16. G. Pantaleo, H. Soudeyns, J. F. Demarest, M. Vaccarezza, C. Graziosi, S. Paolucci, M. B. Daucher, O. J. Cohen, F. Denis, W. E. Biddison, R. P. Sekaly, A. S. Fauci, Accumulation of human immunodeficiency virus-specific cytotoxic T lymphocytes away from the predominant site of virus replication during primary infection. Eur. J. Immunol. 27, 3166-3173 (1997).
17. O. Devergne, M. Peuchmaur, M.-C. Crevon, J. A. Trapani, M.-C. Maillot, P. Galanaud, D. Emilie, Activation of cytotoxic cells in hyperplastic lymph nodes from HIV-infected patients. AIDS 5, 1071-1079 (1991).
18. K. Tenner-Rácz, P. Rácz, M. Dietrich, P. Kern, G. Janossy, F. Veronese-Dimarzo, D. Klatzmann, J. C. Gluckman, M. Popovic, Monoclonal antibodies to human immunodeficiency virus: Their relation to the patterns of lymph node changes in persistent generalized lymphadenopathy and AIDS. AIDS 1, 95-104 (1987).
19. K. Tenner-Racz, P. Racz, C. Thomé, C. G. Meyer, P. J. Anderson, S. F. Schlossman, N. L. Letvin, Cytotoxic effector cell granules recognized by the monoclonal antibody TIA-1 are present in CD8+ lymphocytes in lymph nodes of human immunodeficiency virus-1-infected patients. Am. J. Pathol. 142, 1750-1758 (1993).
20. A. Hosmalin, A. Samri, M.-J. Dumaurier, Y. Dudoit, E. Oksenhendler, M. Karmochkine, B. Autran, S. Wain-Hobson, R. Cheynier, HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients. Blood 97, 2695-2701 (2001).
21. S. J. Brodie, D. A. Lewinsohn, B. K. Patterson, D. Jiyamapa, J. Krieger, L. Corey, P. D. Greenberg, S. R. Riddell, In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nat. Med. 5, 34-41 (1999).
22. Y. Fukazawa, H. Park, M. J. Cameron, F. Lefebvre, R. Lum, N. Coombes, E. Mahyari, S. I. Hagen, J. Y. Bae, M. D. Reyes III, T. Swanson, A. W. Legasse, A. Sylwester, S. G. Hansen, A. T. Smith, P. Stafova, R. Shoemaker, Y. Li, K. Oswald, M. K. Axthelm, A. McDermott, G. Ferrari, D. C. Montefiori, P. T. Edlefsen, M. Piatak Jr., J. D. Lifson, R. P. Sékaly, L. J. Picker, Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines. Nat. Med. 18, 1673-1681 (2012).
23. P. A. Mudd, M. A. Martins, A. J. Ericsen, D. C. Tully, K. A. Power, A. T. Bean, S. M. Piaskowski, L. Duan, A. Seese, A. D. Gladden, K. L. Weisgrau, J. R. Furlott, Y.-I. Kim, M. G. Veloso de Santana, E. Rakasz, S. Capuano III, N. A. Wilson, M. C. Bonaldo, R. Galler, D. B. Allison, M. Piatak Jr., A. T. Haase, J. D. Lifson, T. M. Allen, D. I. Watkins, Vaccineinduced CD8+ T cells control AIDS virus replication. Nature 491, 129-133 (2012).
24. J. Berg, E. Lötscher, K. S. Steimer, D. J. Capon, J. Baenziger, H.-M. Jäck, M. Wabl, Bispecific antibodies that mediate killing of cells infected with human immunodeficiency virus of any strain. Proc. Natl. Acad. Sci. U.S.A. 88, 4723-4727 (1991).
25. S. M. Chamow, D. Z. Zhang, X. Y. Tan, S. M. Mhatre, S. A. Marsters, D. H. Peers, R. A. Byrn, A. Ashkenazi, R. P. Junghans, A humanized, bispecific immunoadhesin-antibody that retargets CD3+ effectors to kill HIV-1-infected cells. J. Immunol. 153, 4268-4280 (1994).
26. R. Bargou, E. Leo, G. Zugmaier, M. Klinger, M. Goebeler, S. Knop, R. Noppeney, A. Viardot, G. Hess, M. Schuler, H. Einsele, C. Brandl, A. Wolf, P. Kirchinger, P. Klappers, M. Schmidt, G. Riethmuller, C. Reinhardt, P. A. Baeuerle, P. Kufer, Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 321, 974-977 (2008).
27. J. A. M. Sung, J. Pickeral, L. Liu, S. A. Stanfield-Oakley, C.-Y. K. Lam, C. Garrido, J. Pollara, C. LaBranche, M. Bonsignori, M. A. Moody, Y. Yang, R. Parks, N. Archin, B. Allard, J. Kirchherr, J. D. Kuruc, C. L. Gay, M. S. Cohen, C. Ochsenbauer, K. Soderberg, H.-X. Liao, D. Montefiori, P. Moore, S. Johnson, S. Koenig, B. F. Haynes, J. L. Nordstrom, D. M. Margolis, G. Ferrari, Dual-affinity re-targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells. J. Clin. Invest. 125, 4077-4090 (2015).
28. D. D. Sloan, C.-Y. K. Lam, A. Irrinki, L. Liu, A. Tsai, C. S. Pace, J. Kaur, J. P. Murry, M. Balakrishnan, P. A. Moore, S. Johnson, J. L. Nordstrom, T. Cihlar, S. Koenig, Targeting HIV reservoir in infected CD4 T cells by dual-affinity re-targeting molecules (DARTs) that bind HIV envelope and recruit cytotoxic T cells. PLOS Pathog. 11, e1005233 (2015).
29. R. S. Rudicell, Y. D. Kwon, S.-Y. Ko, A. Pegu, M. K. Louder, I. S. Georgiev, X. Wu, J. Zhu, J. C. Boyington, X. Chen, W. Shi, Z.-y. Yang, N. A. Doria-Rose, K. McKee, S. O'Dell, S. D. Schmidt, G.-Y. Chuang, A. Druz, C. Soto, Y. Yang, B. Zhang, T. Zhou, J.-P. Todd, K. E. Lloyd, J. Eudailey, K. E. Roberts, B. R. Donald, R. T. Bailer, J. Ledgerwood; NISC Comparative Sequencing Program, J. C. Mullikin, L. Shapiro, R. A. Koup, B. S. Graham, M. C. Nason, M. Connors, B. F. Haynes, S. S. Rao, M. Roederer, P. D. Kwong, J. R. Mascola, G. J. Nabel, Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. J. Virol. 88, 12669-12682 (2014).
30. A. Pegu, M. Asokan, L. Wu, K. Wang, J. Hataye, J. P. Casazza, X. Guo, W. Shi, I. Georgiev, T. Zhou, X. Chen, S. O'Dell, J.-P. Todd, P. D. Kwong, S. S. Rao, Z.-y. Yang, R. A. Koup, J. R. Mascola, G. J. Nabel, Activation and lysis of human CD4 cells latently infected with HIV-1. Nat. Commun. 6, 8447 (2015).
31. N. M. Haynes, C. D. C. Allen, R. Lesley, K. M. Ansel, N. Killeen, J. G. Cyster, Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation. J. Immunol. 179, 5099-5108 (2007).
32. M. Y. Gerner, W. Kastenmuller, I. Ifrim, J. Kabat, R. N. Germain, Histo-cytometry: A method for highly multiplex quantitative tissue imaging analysis applied to dendritic cell subset microanatomy in lymph nodes. Immunity 37, 364-376 (2012).
33. H. Qi, W. Kastenmüller, R. N. Germain, Spatiotemporal basis of innate and adaptive immunity in secondary lymphoid tissue. Annu. Rev. Cell Dev. Biol. 30, 141-167 (2014).
34. S. Pallikkuth, L. Micci, Z. S. Ende, R. I. Iriele, B. Cervasi, B. Lawson, C. S. McGary, K. A. Rogers, J. G. Else, G. Silvestri, K. Easley, J. D. Estes, F. Villinger, S. Pahwa, M. Paiardini, Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21. PLOS Pathog. 9, e1003471 (2013).
35. K. M. Ansel, V. N. Ngo, P. L. Hyman, S. A. Luther, R. Förster, J. D. Sedgwick, J. L. Browning, M. Lipp, J. G. Cyster, A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406, 309-314 (2000).
36. M. Zeng, A. J. Smith, S. W. Wietgrefe, P. J. Southern, T. W. Schacker, C. S. Reilly, J. D. Estes, G. F. Burton, G. Silvestri, J. D. Lifson, J. V. Carlis, A. T. Haase, Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J. Clin. Invest. 121, 998-1008 (2011).
37. T. W. Schacker, C. Reilly, G. J. Beilman, J. Taylor, D. Skarda, D. Krason, M. Larson, A. T. Haase, Amount of lymphatic tissue fibrosis in HIV infection predicts magnitude of HAART-associated change in peripheral CD4 cell count. AIDS 19, 2169-2171 (2005).
38. S. Collins, A. Waickman, A. Basson, A. Kupfer, J. D. Licht, M. R. Horton, J. D. Powell, Regulation of CD4+ and CD8+ effector responses by Sprouty-1. PLOS ONE 7, e49801 (2012).
39. B. Liu, L. Qu, S. Yan, Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell Int. 15, 106 (2015).
40. K. D. Omilusik, J. A. Best, B. Yu, S. Goossens, A. Weidemann, J. V. Nguyen, E. Seuntjens, A. Stryjewska, C. Zweier, R. Roychoudhuri, L. Gattinoni, L. M. Bird, Y. Higashi, H. Kondoh, D. Huylebroeck, J. Haigh, A. W. Goldrath, Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection. J. Exp. Med. 212, 2027-2039 (2015).
41. L. Gattinoni, Y. Ji, N. P. Restifo, Wnt/b-catenin signaling in T-cell immunity and cancer immunotherapy. Clin. Cancer Res. 16, 4695-4701 (2010).
42. M. R. Betts, M. C. Nason, S. M. West, S. C. De Rosa, S. A. Migueles, J. Abraham, M. M. Lederman, J. M. Benito, P. A. Goepfert, M. Connors, M. Roederer, R. A. Koup, HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107, 4781-4789 (2006).
43. T. Yamamoto, D. A. Price, J. P. Casazza, G. Ferrari, M. Nason, P. K. Chattopadhyay, M. Roederer, E. Gostick, P. D. Katsikis, D. C. Douek, R. Haubrich, C. Petrovas, R. A. Koup, Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood 117, 4805-4815 (2011).
44. A. R. Hersperger, G. Makedonas, M. R. Betts, Flow cytometric detection of perforin upregulation in human CD8 T cells. Cytometry A 73, 1050-1057 (2008).
45. G. Makedonas, N. Hutnick, D. Haney, A. C. Amick, J. Gardner, G. Cosma, A. R. Hersperger, D. Dolfi, E. J. Wherry, G. Ferrari, M. R. Betts, Perforin and IL-2 upregulation define qualitative differences among highly functional virus-specific human CD8+ T cells. PLOS Pathog. 6, e1000798 (2010).
46. A. R. Martin, R. F. Siliciano, Progress toward HIV eradication: Case reports, current efforts, and the challenges associated with cure. Annu. Rev. Med. 67, 215-228 (2016).
47. D. H. Barouch, S. G. Deeks, Immunologic strategies for HIV-1 remission and eradication. Science 345, 169-174 (2014).
48. J. D. Estes, Pathobiology of HIV/SIV-associated changes in secondary lymphoid tissues. Immunol. Rev. 254, 65-77 (2013).
49. N. R. Klatt, N. Chomont, D. C. Douek, S. G. Deeks, Immune activation and HIV persistence: Implications for curative approaches to HIV infection. Immunol. Rev. 254, 326-342 (2013).
50. D. L. Regidor, R. Detels, E. C. Breen, D. P. Widney, L. P. Jacobson, F. Palella, C. R. Rinaldo, J. H. Bream, O. Martínez-Maza, Effect of highly active antiretroviral therapy on biomarkers of B-lymphocyte activation and inflammation. AIDS 25, 303-314 (2011).
51. K. Deng, M. Pertea, A. Rongvaux, L. Wang, C. M. Durand, G. Ghiaur, J. Lai, H. L. McHugh, H. Hao, H. Zhang, J. B. Margolick, C. Gurer, A. J. Murphy, D. M. Valenzuela, G. D. Yancopoulos, S. G. Deeks, T. Strowig, P. Kumar, J. D. Siliciano, S. L. Salzberg, R. A. Flavell, L. Shan, R. F. Siliciano, Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517, 381-385 (2015).
52. E. C. Stack, C. Wang, K. A. Roman, C. C. Hoyt, Multiplexed immunohistochemistry, imaging, and quantitation: A review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis. Methods 70, 46-58 (2014).
53. A. Cooper, M. Garcia, C. Petrovas, T. Yamamoto, R. A. Koup, G. J. Nabel, HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature 498, 376-379 (2013).
54. S. Palmer, A. P. Wiegand, F. Maldarelli, H. Bazmi, J. M. Mican, M. Polis, R. L. Dewar, A. Planta, S. Liu, J. A. Metcalf, J. W. Mellors, J. M. Coffin, New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J. Clin. Microbiol. 41, 4531-4536 (2003).
55. D. C. Douek, J. M. Brenchley, M. R. Betts, D. R. Ambrozak, B. J. Hill, Y. Okamoto, J. P. Casazza, J. Kuruppu, K. Kunstman, S. Wolinsky, Z. Grossman, M. Dybul, A. Oxenius, D. A. Price, M. Connors, R. A. Koup, HIV preferentially infects HIV-specific CD4+ T cells. Nature 417, 95-98 (2002).
56. R. M. Lynch, E. Boritz, E. E. Coates, A. DeZure, P. Madden, P. Costner, M. E. Enama, S. Plummer, L. Holman, C. S. Hendel, I. Gordon, J. Casazza, M. Conan-Cibotti, S. A. Migueles, R. Tressler, R. T. Bailer, A. McDermott, S. Narpala, S. O'Dell, G. Wolf, J. D. Lifson, B. A. Freemire, R. J. Gorelick, J. P. Pandey, S. Mohan, N. Chomont, R. Fromentin, T.-W. Chun, A. S. Fauci, R. M. Schwartz, R. A. Koup, D. C. Douek, Z. Hu, E. Capparelli, B. S. Graham, J. R. Mascola, J. E. Ledgerwood, VRC 601 Study Team, Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci. Transl. Med. 7, 319ra206 (2015).
57. N. G. Sandler, S. E. Bosinger, J. D. Estes, R. T. R. Zhu, G. K. Tharp, E. Boritz, D. Levin, S. Wijeyesinghe, K. N. Makamdop, G. Q. del Prete, B. J. Hill, J. K. Timmer, E. Reiss, G. Yarden, S. Darko, E. Contijoch, J. P. Todd, G. Silvestri, M. Nason, R. B. Norgren Jr., B. F. Keele, S. Rao, J. A. Langer, J. D. Lifson, G. Schreiber, D. C. Douek, Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511, 601-605 (2014).
58. C. Trapnell, L. Pachter, S. L. Salzberg, TopHat: Discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105-1111 (2009).
59. C. Trapnell, B. A. Williams, G. Pertea, A. Mortazavi, G. Kwan, M. J. van Baren, S. L. Salzberg, B. J. Wold, L. Pachter, Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511-515 (2010).