#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies


Autoři: Wenwen Bi aff001;  Wei Xu aff001;  Liang Cheng aff002;  Jing Xue aff003;  Qian Wang aff001;  Fei Yu aff001;  Shuai Xia aff001;  Qi Wang aff002;  Guangming Li aff002;  Chuan Qin aff003;  Lu Lu aff001;  Lishan Su aff002;  Shibo Jiang aff001
Působiště autorů: Key Laboratory of Medical Molecular Virology of MOE/NHC/CAMS, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China aff001;  Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America aff002;  Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Re-emerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Com aff003;  Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America aff004
Vyšlo v časopise: IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008082
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008082

Souhrn

The clinical application of conventional peptide drugs, such as the HIV-1 fusion inhibitor enfuvirtide, is limited by their short half-life in vivo. To overcome this limitation, we developed a new strategy to extend the in vivo half-life of a short HIV-1 fusion inhibitory peptide, CP24, by fusing it with the human IgG Fc-binding peptide (IBP). The newly engineered peptide IBP-CP24 exhibited potent and broad anti-HIV-1 activity with IC50 values ranging from 0.2 to 173.7 nM for inhibiting a broad spectrum of HIV-1 strains with different subtypes and tropisms, including those resistant to enfuvirtide. Most importantly, its half-life in the plasma of rhesus monkeys was 46.1 h, about 26- and 14-fold longer than that of CP24 (t1/2 = 1.7 h) and enfuvirtide (t1/2 = 3 h), respectively. IBP-CP24 intravenously administered in rhesus monkeys could not induce significant IBP-CP24-specific antibody response and it showed no obvious in vitro or in vivo toxicity. In the prophylactic study, humanized mice pretreated with IBP-CP24 were protected from HIV-1 infection. As a therapeutic treatment, coadministration of IBP-CP24 and normal human IgG to humanized mice with chronic HIV-1 infection resulted in a significant decrease of plasma viremia. Combining IBP-CP24 with a broad neutralizing antibody (bNAb) targeting CD4-binding site (CD4bs) in gp120 or a membrane proximal external region (MPER) in gp41 exhibited synergistic effect, resulting in significant dose-reduction of the bNAb and IBP-CP24. These results suggest that IBP-CP24 has the potential to be further developed as a new HIV-1 fusion inhibitor-based, long-acting anti-HIV drug that can be used alone or in combination with a bNAb for treatment and prevention of HIV-1 infection.

Klíčová slova:

Blood plasma – Cell fusion – Enzyme-linked immunoassays – HIV-1 – Mouse models – Rhesus monkeys – Elimination half-life calculation


Zdroje

1. Yerly S, Kaiser L, Race E, Bru JP, Clavel F, Perrin L. Transmission of antiretroviral-drug-resistant HIV-1 variants. Lancet 1999;354(9180):729–33. doi: 10.1016/S0140-6736(98)12262-6 10475184

2. De Clercq E. Antiviral drugs in current clinical use. J Clin Virol 2004;30(2):115–33. doi: 10.1016/j.jcv.2004.02.009 15125867

3. Jiang S, Lin K, Strick N, Neurath AR. HIV-1 inhibition by a peptide. Nature 1993;365(6442):113. doi: 10.1038/365113a0 8371754

4. Matthews T, Salgo M, Greenberg M, Chung J, DeMasi R, Bolognesi D. Enfuvirtide: the first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes. Nat Rev Drug Discov 2004;3(3):215–25. doi: 10.1038/nrd1331 15031735

5. Fletcher CV. Enfuvirtide, a new drug for HIV infection. Lancet 2003;361(9369):1577–8. doi: 10.1016/S0140-6736(03)13323-5 12747873

6. Steinbrook R. HIV infection—a new drug and new costs. N Engl J Med 2003;348(22):2171–2. doi: 10.1056/NEJMp030043 12773643

7. Lalezari JP, Eron JJ, Carlson M, Cohen C, DeJesus E, Arduino RC, et al. A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy. AIDS 2003;17(5):691–8. doi: 10.1097/00002030-200303280-00007 12646792

8. Stocker H, Kloft C, Plock N, Breske A, Kruse G, Herzmann C, et al. Pharmacokinetics of enfuvirtide in patients treated in typical routine clinical settings. Antimicrob Agents Chemother 2006;50(2):667–73. doi: 10.1128/AAC.50.2.667-673.2006 16436725

9. Kilby JM, Lalezari JP, Eron JJ, Carlson M, Cohen C, Arduino RC, et al. The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults. AIDS Res Hum Retroviruses 2002;18(10):685–93. doi: 10.1089/088922202760072294 12167274

10. Zhang X, Nieforth K, Lang JM, Rouzier-Panis R, Reynes J, Dorr A, et al. Pharmacokinetics of plasma enfuvirtide after subcutaneous administration to patients with human immunodeficiency virus: Inverse Gaussian density absorption and 2-compartment disposition. Clin Pharmacol Ther 2002;72(1):10–9. doi: 10.1067/mcp.2002.125945 12152000

11. Veronese FM, Pasut G. PEGylation, successful approach to drug delivery. Drug Discov Today 2005;10(21):1451–8. doi: 10.1016/S1359-6446(05)03575-0 16243265

12. Harris JM, Martin NE, Modi M. Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet 2001;40(7):539–51. doi: 10.2165/00003088-200140070-00005 11510630

13. Schellekens H, Hennink WE, Brinks V. The immunogenicity of polyethylene glycol: facts and fiction. Pharm Res 2013;30(7):1729–34. doi: 10.1007/s11095-013-1067-7 23673554

14. Garay RP, El-Gewely R, Armstrong JK, Garratty G, Richette P. Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents. Expert Opin Drug Deliv 2012;9(11):1319–23. doi: 10.1517/17425247.2012.720969 22931049

15. Richter AW, Akerblom E. Antibodies against polyethylene glycol produced in animals by immunization with monomethoxy polyethylene glycol modified proteins. Int Arch Allergy Appl Immunol 1983;70(2):124–31. doi: 10.1159/000233309 6401699

16. Rath T, Baker K, Dumont JA, Peters RT, Jiang H, Qiao SW, et al. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit Rev Biotechnol 2015;35(2):235–54. doi: 10.3109/07388551.2013.834293 24156398

17. Chuang VT, Kragh-Hansen U, Otagiri M. Pharmaceutical strategies utilizing recombinant human serum albumin. Pharm Res 2002;19(5):569–77. doi: 10.1023/a:1015396825274 12069157

18. Sockolosky JT, Kivimae S, Szoka FC. Fusion of a short peptide that binds immunoglobulin G to a recombinant protein substantially increases its plasma half-life in mice. PLoS One 2014;9(7):e102566. doi: 10.1371/journal.pone.0102566 25057984

19. DeLano WL, Ultsch MH, de Vos AM, Wells JA. Convergent solutions to binding at a protein-protein interface. Science 2000;287(5456):1279–83. doi: 10.1126/science.287.5456.1279 10678837

20. Chong H, Qiu Z, Sun J, Qiao Y, Li X, He Y. Two M-T hook residues greatly improve the antiviral activity and resistance profile of the HIV-1 fusion inhibitor SC29EK. Retrovirology 2014;11:40. doi: 10.1186/1742-4690-11-40 24884671

21. Chong H, Yao X, Qiu Z, Sun J, Zhang M, Waltersperger S, et al. Short-peptide fusion inhibitors with high potency against wild-type and enfuvirtide-resistant HIV-1. FASEB J 2013;27(3):1203–13. doi: 10.1096/fj.12-222547 23233535

22. Dai SJ, Dou GF, Qiang XH, Song HF, Tang ZM, Liu DS, et al. Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro. Acta Pharmacol Sin 2005;26(10):1274–80. doi: 10.1111/j.1745-7254.2005.00163.x 16174446

23. Chong H, Wu X, Su Y, He Y. Development of potent and long-acting HIV-1 fusion inhibitors. AIDS 2016;30(8):1187–96. doi: 10.1097/QAD.0000000000001073 26919736

24. Chong H, Xue J, Xiong S, Cong Z, Ding X, Zhu Y, et al. A Lipopeptide HIV-1/2 Fusion Inhibitor with Highly Potent In Vitro, Ex Vivo, and In Vivo Antiviral Activity. J Virol 2017;91(11).

25. Chong H, Xue J, Zhu Y, Cong Z, Chen T, Guo Y, et al. Design of Novel HIV-1/2 Fusion Inhibitors with High Therapeutic Efficacy in Rhesus Monkey Models. J Virol 2018;92(16).

26. Su S, Rasquinha G, Du L, Wang Q, Xu W, Li W, et al. A Peptide-Based HIV-1 Fusion Inhibitor with Two Tail-Anchors and Palmitic Acid Exhibits Substantially Improved In Vitro and Ex Vivo Anti-HIV-1 Activity and Prolonged In Vivo Half-Life. Molecules 2019;24(6).

27. Dwyer JJ, Wilson KL, Davison DK, Freel SA, Seedorff JE, Wring SA, et al. Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus. Proc Natl Acad Sci U S A 2007;104(31):12772–7. doi: 10.1073/pnas.0701478104 17640899

28. Miro JM, Cofan F, Trullas JC, Manzardo C, Cervera C, Tuset M, et al. Renal dysfunction in the setting of HIV/AIDS. Curr HIV/AIDS Rep 2012;9(3):187–99. doi: 10.1007/s11904-012-0125-9 22706955

29. Truter D, Chellan N, Strijdom H, Webster I, Rawstorne J, Kotze SH. Histomorphological changes in the pancreas and kidney and histopathological changes in the liver in male Wistar rats on antiretroviral therapy and melatonin treatment. Acta Histochem 2018;120(4):347–355. doi: 10.1016/j.acthis.2018.03.006 29605225

30. Wondifraw BH, Tegene B, Gebremichael M, Birhane G, Kedir W, Biadgo B. Assessment of the effect of antiretroviral therapy on renal and liver functions among HIV-infected patients: a retrospective study. HIV AIDS (Auckl) 2017;9:1–7.

31. Zhang L, Su L. HIV-1 immunopathogenesis in humanized mouse models. Cell Mol Immunol 2012;9(3):237–44. doi: 10.1038/cmi.2012.7 22504952

32. Bardhi A, Wu Y, Chen W, Li W, Zhu Z, Zheng JH, et al. Potent In Vivo NK Cell-Mediated Elimination of HIV-1-Infected Cells Mobilized by a gp120-Bispecific and Hexavalent Broadly Neutralizing Fusion Protein. J Virol 2017;91(20).

33. Sun Z, Zhu Y, Wang Q, Ye L, Dai Y, Su S, et al. An immunogen containing four tandem 10E8 epitope repeats with exposed key residues induces antibodies that neutralize HIV-1 and activates an ADCC reporter gene. Emerg Microbes Infect 2016;5:e65. doi: 10.1038/emi.2016.86 27329850

34. Bruel T, Guivel-Benhassine F, Amraoui S, Malbec M, Richard L, Bourdic K, et al. Elimination of HIV-1-infected cells by broadly neutralizing antibodies. Nat Commun 2016;7:10844. doi: 10.1038/ncomms10844 26936020

35. Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006;58(3):621–81. doi: 10.1124/pr.58.3.10 16968952

36. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27–55. doi: 10.1016/0065-2571(84)90007-4 6382953

37. Huang J, Kang BH, Ishida E, Zhou T, Griesman T, Sheng Z, et al. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. Immunity 2016;45(5):1108–1121. doi: 10.1016/j.immuni.2016.10.027 27851912

38. Rudicell RS, Kwon YD, Ko SY, Pegu A, Louder MK, Georgiev IS, et al. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. J Virol 2014;88(21):12669–82. doi: 10.1128/JVI.02213-14 25142607

39. Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 2012;491(7424):406–12. doi: 10.1038/nature11544 23151583

40. Zhao Q, Ma L, Jiang S, Lu H, Liu S, He Y, et al. Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4. Virology 2005;339(2):213–25. doi: 10.1016/j.virol.2005.06.008 15996703

41. Liu S, Lu H, Niu J, Xu Y, Wu S, Jiang S. Different from the HIV fusion inhibitor C34, the anti-HIV drug Fuzeon (T-20) inhibits HIV-1 entry by targeting multiple sites in gp41 and gp120. J Biol Chem 2005;280(12):11259–73. doi: 10.1074/jbc.M411141200 15640162

42. Zhu X, Zhu Y, Ye S, Wang Q, Xu W, Su S, et al. Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy. Sci Rep 2015;5:13028. doi: 10.1038/srep13028 26286358

43. Patel IH, Zhang X, Nieforth K, Salgo M, Buss N. Pharmacokinetics, pharmacodynamics and drug interaction potential of enfuvirtide. Clin Pharmacokinet 2005;44(2):175–86. doi: 10.2165/00003088-200544020-00003 15656696

44. Hamburger AE, Kim S, Welch BD, Kay MS. Steric accessibility of the HIV-1 gp41 N-trimer region. J Biol Chem 2005;280(13):12567–72. doi: 10.1074/jbc.M412770200 15657041

45. Eckert DM, Shi Y, Kim S, Welch BD, Kang E, Poff ES, et al. Characterization of the steric defense of the HIV-1 gp41 N-trimer region. Protein Sci 2008;17(12):2091–100. doi: 10.1110/ps.038273.108 18802030

46. Dewji NN, Azar MR, Hanson LR, Frey IW, Morimoto BH, Johnson D. Pharmacokinetics in Rat of P8, a Peptide Drug Candidate for the Treatment of Alzheimer's Disease: Stability and Delivery to the Brain. J Alzheimers Dis Rep 2018;2(1):169–179. doi: 10.3233/ADR-180078 30480260

47. Chew MF, Poh KS, Poh CL. Peptides as Therapeutic Agents for Dengue Virus. Int J Med Sci 2017;14(13):1342–1359. doi: 10.7150/ijms.21875 29200948

48. Yu Y, Deng YQ, Zou P, Wang Q, Dai Y, Yu F, et al. A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses. Nat Commun 2017;8:15672. doi: 10.1038/ncomms15672 28742068

49. Jones JC, Turpin EA, Bultmann H, Brandt CR, Schultz-Cherry S. Inhibition of influenza virus infection by a novel antiviral peptide that targets viral attachment to cells. J Virol 2006;80(24):11960–7. doi: 10.1128/JVI.01678-06 17005658

50. Albiol MV, Castilla V. Antiviral activity of antimicrobial cationic peptides against Junin virus and herpes simplex virus. Int J Antimicrob Agents 2004;23(4):382–9. doi: 10.1016/j.ijantimicag.2003.07.022 15081088

51. Kilby JM, Hopkins S, Venetta TM, DiMassimo B, Cloud GA, Lee JY, et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 1998;4(11):1302–7. doi: 10.1038/3293 9809555

52. Finan B, Clemmensen C, Muller TD. Emerging opportunities for the treatment of metabolic diseases: Glucagon-like peptide-1 based multi-agonists. Mol Cell Endocrinol 2015;418 Pt 1:42–54.

53. Hui H, Farilla L, Merkel P, Perfetti R. The short half-life of glucagon-like peptide-1 in plasma does not reflect its long-lasting beneficial effects. Eur J Endocrinol 2002;146(6):863–9. doi: 10.1530/eje.0.1460863 12039708

54. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev 2016;99(Pt A):28–51. doi: 10.1016/j.addr.2015.09.012 26456916

55. Yang Q, Lai SK. Anti-PEG immunity: emergence, characteristics, and unaddressed questions. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2015;7(5):655–77. doi: 10.1002/wnan.1339 25707913

56. Koide H, Asai T, Hatanaka K, Urakami T, Ishii T, Kenjo E, et al. Particle size-dependent triggering of accelerated blood clearance phenomenon. Int J Pharm 2008;362(1–2):197–200. doi: 10.1016/j.ijpharm.2008.06.004 18586076

57. Ishida T, Maeda R, Ichihara M, Irimura K, Kiwada H. Accelerated clearance of PEGylated liposomes in rats after repeated injections. J Control Release 2003;88(1):35–42. doi: 10.1016/s0168-3659(02)00462-5 12586501

58. Laverman P, Brouwers AH, Dams ET, Oyen WJ, Storm G, van Rooijen N, et al. Preclinical and clinical evidence for disappearance of long-circulating characteristics of polyethylene glycol liposomes at low lipid dose. J Pharmacol Exp Ther 2000;293(3):996–1001. 10869403

59. Ivens IA, Achanzar W, Baumann A, Brandli-Baiocco A, Cavagnaro J, Dempster M, et al. PEGylated Biopharmaceuticals: Current Experience and Considerations for Nonclinical Development. Toxicol Pathol 2015;43(7):959–83. doi: 10.1177/0192623315591171 26239651

60. Pelegri-O'Day EM, Lin EW, Maynard HD. Therapeutic protein-polymer conjugates: advancing beyond PEGylation. J Am Chem Soc 2014;136(41):14323–32. doi: 10.1021/ja504390x 25216406

61. Young MA, Malavalli A, Winslow N, Vandegriff KD, Winslow RM. Toxicity and hemodynamic effects after single dose administration of MalPEG-hemoglobin (MP4) in rhesus monkeys. Transl Res 2007;149(6):333–42. doi: 10.1016/j.trsl.2006.09.007 17543852

62. Bendele A, Seely J, Richey C, Sennello G, Shopp G. Short communication: renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol Sci 1998;42(2):152–7. doi: 10.1006/toxs.1997.2396 9579027

63. Su S, Zhu Y, Ye S, Qi Q, Xia S, Ma Z, et al. Creating an Artificial Tail Anchor as a Novel Strategy To Enhance the Potency of Peptide-Based HIV Fusion Inhibitors. J Virol 2017;91(1).

64. Lugada ES, Mermin J, Asjo B, Kaharuza F, Downing R, Langeland N, et al. Immunoglobulin levels amongst persons with and without human immunodeficiency virus type 1 infection in Uganda and Norway. Scand J Immunol 2004;59(2):203–8. doi: 10.1111/j.0300-9475.2004.01376.x 14871298

65. Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 1983;309(8):453–8. doi: 10.1056/NEJM198308253090803 6224088

66. Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F, Oliveira TY, et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 2011;333(6049):1633–7. doi: 10.1126/science.1207227 21764753

67. Mouquet H, Scharf L, Euler Z, Liu Y, Eden C, Scheid JF, et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A 2012;109(47):E3268–77. doi: 10.1073/pnas.1217207109 23115339

68. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 2009;326(5950):285–9. doi: 10.1126/science.1178746 19729618

69. Halper-Stromberg A, Lu CL, Klein F, Horwitz JA, Bournazos S, Nogueira L, et al. Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell 2014;158(5):989–999. doi: 10.1016/j.cell.2014.07.043 25131989

70. Casadevall A, Dadachova E, Pirofski LA. Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2004;2(9):695–703. doi: 10.1038/nrmicro974 15372080

71. Lalezari JP, Latiff GH, Brinson C, Echevarria J, Trevino-Perez S, Bogner JR, et al. Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial. Lancet HIV 2015;2(10):e427–37. doi: 10.1016/S2352-3018(15)00177-0 26423650

72. Nowicka-Sans B, Gong YF, McAuliffe B, Dicker I, Ho HT, Zhou N, et al. In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068. Antimicrob Agents Chemother 2012;56(7):3498–507. doi: 10.1128/AAC.00426-12 22547625

73. Zhang Y, Chapman JH, Ulcay A, Sutton RE. Neutralization Synergy between HIV-1 Attachment Inhibitor Fostemsavir and Anti-CD4 Binding Site Broadly Neutralizing Antibodies against HIV. J Virol 2018.

74. He Y, Cheng J, Lu H, Li J, Hu J, Qi Z, et al. Potent HIV fusion inhibitors against Enfuvirtide-resistant HIV-1 strains. Proc Natl Acad Sci U S A 2008;105(42):16332–7. doi: 10.1073/pnas.0807335105 18852475

75. Liu S, Lu H, Niu J, Xu Y, Wu S, Jiang S. Different from the HIV fusion inhibitor C34, the anti-HIV drug Fuzeon (T-20) inhibits HIV-1 entry by targeting multiple sites in gp41 and gp120. J Biol Chem 2005;280(12):11259–73. doi: 10.1074/jbc.M411141200 15640162

76. Lu L, Pan C, Li Y, Lu H, He W, Jiang S. A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains. Retrovirology 2012;9:104. doi: 10.1186/1742-4690-9-104 23217195

77. Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. Atomic structure of the ectodomain from HIV-1 gp41. Nature 1997;387(6631):426–30. doi: 10.1038/387426a0 9163431

78. Jiang SB, Lin K, Neurath AR. Enhancement of human immunodeficiency virus type 1 infection by antisera to peptides from the envelope glycoproteins gp120/gp41. J Exp Med 1991;174(6):1557–63. doi: 10.1084/jem.174.6.1557 1836013

79. Wang Q, Bi W, Zhu X, Li H, Qi Q, Yu F, et al. Nonneutralizing Antibodies Induced by the HIV-1 gp41 NHR Domain Gain Neutralizing Activity in the Presence of the HIV Fusion Inhibitor Enfuvirtide: a Potential Therapeutic Vaccine Strategy. J Virol 2015;89(13):6960–4. doi: 10.1128/JVI.00791-15 25903343

80. Zhao Q, Ernst JT, Hamilton AD, Debnath AK, Jiang S. XTT formazan widely used to detect cell viability inhibits HIV type 1 infection in vitro by targeting gp41. AIDS Res Hum Retroviruses 2002;18(14):989–97. doi: 10.1089/08892220260235353 12396451

81. Tong P, Lu Z, Chen X, Wang Q, Yu F, Zou P, et al. An engineered HIV-1 gp41 trimeric coiled coil with increased stability and anti-HIV-1 activity: implication for developing anti-HIV microbicides. J Antimicrob Chemother 2013;68(11):2533–44. doi: 10.1093/jac/dkt230 23794600

82. He Y, Xiao Y, Song H, Liang Q, Ju D, Chen X, et al. Design and evaluation of sifuvirtide, a novel HIV-1 fusion inhibitor. J Biol Chem 2008;283(17):11126–34. doi: 10.1074/jbc.M800200200 18303020

83. Kim M, Song L, Moon J, Sun ZY, Bershteyn A, Hanson M, et al. Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry. J Biol Chem 2013;288(44):31888–901. doi: 10.1074/jbc.M113.494609 24047898

84. Yu F, Lu L, Liu Q, Yu X, Wang L, He E, et al. ADS-J1 inhibits HIV-1 infection and membrane fusion by targeting the highly conserved pocket in the gp41 NHR-trimer. Biochim Biophys Acta 2014;1838(5):1296–305. doi: 10.1016/j.bbamem.2013.12.022 24388952

85. Allen GD. MODFIT: a pharmacokinetics computer program. Biopharm Drug Dispos 1990;11(6):477–98. doi: 10.1002/bdd.2510110603 2207299

86. Yao X, Chong H, Zhang C, Waltersperger S, Wang M, Cui S, et al. Broad antiviral activity and crystal structure of HIV-1 fusion inhibitor sifuvirtide. J Biol Chem 2012;287(9):6788–96. doi: 10.1074/jbc.M111.317883 22228771

87. Li G, Cheng M, Nunoya J, Cheng L, Guo H, Yu H, et al. Plasmacytoid dendritic cells suppress HIV-1 replication but contribute to HIV-1 induced immunopathogenesis in humanized mice. PLoS Pathog 2014;10(7):e1004291. doi: 10.1371/journal.ppat.1004291 25077616

88. Cheng L, Ma J, Li J, Li D, Li G, Li F, et al. Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. J Clin Invest 2017;127(1):269–279. doi: 10.1172/JCI90745 27941247

89. Spiegelberg HL, Fishkin BG, Grey HM. Catabolism of human gammaG-immunoglobulins of different heavy chain subclasses. I. Catabolism of gammaG-myeloma proteins in man. J Clin Invest 1968;47(10):2323–30. doi: 10.1172/JCI105917 4175542

Štítky
Hygiena a epidemiologie Infekční lékařství Laboratoř

Článek vyšel v časopise

PLOS Pathogens


2019 Číslo 12
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#