HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry

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• 作者：Michael Roche (1) (2)
  Martin R Jakobsen (1) (3)
  Anne Ellett (1)
  Hamid Salimiseyedabad (1)
  Becky Jubb (4)
  Mike Westby (4)
  Benhur Lee (5)
  Sharon R Lewin (1) (2) (6)
  Melissa J Churchill (1) (7)
  Paul R Gorry (1) (2) (8)
  
• 刊名：Retrovirology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：8
• 期：1
• 全文大小：471KB
• 参考文献：1. Gorry PR, Ancuta P: Coreceptors and HIV-1 pathogenesis. / Current HIV/AIDS Reports 2011, 8:45鈥?3. CrossRef
  2. Dragic T, Trkola A, Thompson DA, Cormier EG, Kajumo FA, Maxwell E, Lin SW, Ying W, Smith SO, Sakmar TP, Moore JP: A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. / Proc Natl Acad Sci USA 2000, 97:5639鈥?644. CrossRef
  3. Seibert C, Ying W, Gavrilov S, Tsamis F, Kuhmann SE, Palani A, Tagat JR, Clader JW, McCombie SW, Baroudy BM, / et al.: Interaction of small molecule inhibitors of HIV-1 entry with CCR5. / Virology 2006, 349:41鈥?4. CrossRef
  4. Tsamis F, Gavrilov S, Kajumo F, Seibert C, Kuhmann S, Ketas T, Trkola A, Palani A, Clader JW, Tagat JR, / et al.: Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry. / J Virol 2003, 77:5201鈥?208. CrossRef
  5. Gorry PR, Ellett A, Lewin SR: Maraviroc. In / Kucers' The Use of Antibiotics. 6th edition. Edited by: Grayson L, Crowe S, McCarthy J, Mills J, Mouton J, Norrby SR, Paterson D, Pfaller M. London: Hodder & Stoughton Ltd; 2010:2869鈥?876.
  6. Westby M, Lewis M, Whitcomb J, Youle M, Pozniak AL, James IT, Jenkins TM, Perros M, van der Ryst E: Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. / J Virol 2006, 80:4909鈥?920. CrossRef
  7. Berro R, Sanders RW, Lu M, Klasse PJ, Moore JP: Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry. / PLoS Pathog 2009, 5:e1000548. CrossRef
  8. Kitrinos KM, Amrine-Madsen H, Irlbeck DM, Word JM, Demarest JF: Virologic failure in therapy-naive subjects on aplaviroc plus lopinavir-ritonavir: detection of aplaviroc resistance requires clonal analysis of envelope. / Antimicrob Agents Chemother 2009, 53:1124鈥?131. CrossRef
  9. Pfaff JM, Wilen CB, Harrison JE, Demarest JF, Lee B, Doms RW, Tilton JC: HIV-1 resistance to CCR5 antagonists associated with highly efficient use of CCR5 and altered tropism on primary CD4+ T cells. / J Virol 2010, 84:6505鈥?514. CrossRef
  10. Pugach P, Marozsan AJ, Ketas TJ, Landes EL, Moore JP, Kuhmann SE: HIV-1 clones resistant to a small molecule CCR5 inhibitor use the inhibitor-bound form of CCR5 for entry. / Virology 2007, 361:212鈥?28. CrossRef
  11. Pugach P, Ray N, Klasse PJ, Ketas TJ, Michael E, Doms RW, Lee B, Moore JP: Inefficient entry of vicriviroc-resistant HIV-1 via the inhibitor-CCR5 complex at low cell surface CCR5 densities. / Virology 2009, 387:296鈥?02. CrossRef
  12. Tilton JC, Amrine-Madsen H, Miamidian JL, Kitrinos KM, Pfaff J, Demarest JF, Ray N, Jeffrey JL, Labranche CC, Doms RW: HIV type 1 from a patient with baseline resistance to CCR5 antagonists uses drug-bound receptor for entry. / AIDS Res Hum Retroviruses 2010, 26:13鈥?4. CrossRef
  13. Tilton JC, Wilen CB, Didigu CA, Sinha R, Harrison JE, Agrawal-Gamse C, Henning EA, Bushman FD, Martin JN, Deeks SG, Doms RW: A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5. / J Virol 2010, 84:10863鈥?0876. CrossRef
  14. Ogert RA, Hou Y, Ba L, Wojcik L, Qiu P, Murgolo N, Duca J, Dunkle LM, Ralston R, Howe JA: Clinical resistance to vicriviroc through adaptive V3 loop mutations in HIV-1 subtype D gp120 that alter interactions with the N-terminus and ECL2 of CCR5. / Virology 2010, 400:145鈥?55. CrossRef
  15. Roche M, Jakobsen MR, Sterjovski J, Ellett A, Posta F, Lee B, Jubb B, Westby M, Lewin SR, Ramsland PA, / et al.: HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less efficient mechanism of gp120-CCR5 engagement that attenuates macrophage-tropism. / J Virol 2011, 85:4330鈥?342. CrossRef
  16. Westby M, Smith-Burchnell C, Mori J, Lewis M, Mosley M, Stockdale M, Dorr P, Ciaramella G, Perros M: Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. / J Virol 2007, 81:2359鈥?371. CrossRef
  17. Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR: Change in coreceptor use coreceptor use correlates with disease progression in HIV-1--infected individuals. / J Exp Med 1997, 185:621鈥?28. CrossRef
  18. Marozsan AJ, Kuhmann SE, Morgan T, Herrera C, Rivera-Troche E, Xu S, Baroudy BM, Strizki J, Moore JP: Generation and properties of a human immunodeficiency virus type 1 isolate resistant to the small molecule CCR5 inhibitor, SCH-417690 (SCH-D). / Virology 2005, 338:182鈥?99. CrossRef
  19. Pugach P, Ketas TJ, Michael E, Moore JP: Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors. / Virology 2008, 377:401鈥?07. CrossRef
  20. Trkola A, Kuhmann SE, Strizki JM, Maxwell E, Ketas T, Morgan T, Pugach P, Xu S, Wojcik L, Tagat J, / et al.: HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. / Procedings of the National Academy of Sciences USA 2002, 99:395鈥?00. CrossRef
  21. Johnston SH, Lobriz MA, Nguyen S, Lassen K, Delair S, Posta F, Bryson YJ, Arts EJ, Chou T, Lee B: A quantitative affinity-profiling system that reveals distinct CD4/CCR5 usage patterns among human immunodeficiency virus type 1 and simian immunodeficiency virus strains. / Journal of Virology 2009, 83:11016鈥?1026. CrossRef
  22. Lee B, Sharron M, Montaner LJ, Weissman D, Doms RW: Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. / Proc Natl Acad Sci USA 1999, 96:5215鈥?220. CrossRef
  23. Anastassopoulou CG, Ketas TJ, Klasse PJ, Moore JP: Resistance to CCR5 inhibitors caused by sequence changes in the fusion peptide of HIV-1 gp41. / Proc Natl Acad Sci USA 2009, 106:5318鈥?323. CrossRef
  24. Kuhmann SE, Pugach P, Kunstman KJ, Taylor J, Stanfield RL, Snyder A, Strizki JM, Riley J, Baroudy BM, Wilson IA, / et al.: Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor. / J Virol 2004, 78:2790鈥?807. CrossRef
  25. Jakobsen MR, Roche M, Sterjovski J, Ellett A, Posta F, Lee B, Churchill MJ, Gorry PR: Characterisation of the virus-cell interactions by HIV-1 subtype C variants from an antiretroviral therapy-naive subject with baseline resistance to the CCR5 inhibitor maraviroc. / Program and Abstracts of the Keystone Symposium on HIV Evolution, Genomics and Pathogenesis, Whistler 2011. March 20鈥?5, poster 248
  
• 作者单位：Michael Roche (1) (2)
  Martin R Jakobsen (1) (3)
  Anne Ellett (1)
  Hamid Salimiseyedabad (1)
  Becky Jubb (4)
  Mike Westby (4)
  Benhur Lee (5)
  Sharon R Lewin (1) (2) (6)
  Melissa J Churchill (1) (7)
  Paul R Gorry (1) (2) (8)
  
  1. Center for Virology, Burnet Institute, Melbourne, Victoria, Australia
  2. Department of Medicine, Monash University, Melbourne, Victoria, Australia
  3. Department of Medical Microbiology and Immunology, Aarhus University, Aarhus, Denmark
  4. Pfizer Global Research and Development, Sandwich, UK
  5. Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
  6. Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia
  7. Department of Microbiology, Monash University, Melbourne, Victoria, Australia
  8. Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia
  
• ISSN：1742-4690

文摘

Background Maraviroc (MVC) and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by the viral gp120 envelope (Env) glycoproteins. Resistance to CCR5 antagonists results from HIV-1 Env acquiring the ability to utilize the drug-bound conformation of CCR5. Selecting for HIV-1 resistance to CCR5-antagonists in vitro is relatively difficult. However, the CCR5-using CC1/85 strain appears to be uniquely predisposed to acquiring resistance to several CCR5 antagonists in vitro including MVC, vicriviroc and AD101. Findings Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interaction with MVC-bound CCR5. However, this phenotype was only revealed in 293-Affinofile cells and NP2-CD4/CCR5 cells that express very high levels of CCR5, and was masked in TZM-bl, JC53 and U87-CD4/CCR5 cells as well as PBMC, which express comparatively lower levels of CCR5 and which are more commonly used to detect resistance to CCR5 antagonists. Conclusions Env derived from the CC1/85 strain of HIV-1 is inherently capable of a low-affinity interaction with MVC-bound CCR5, which helps explain the relative ease in which CC1/85 can acquire resistance to CCR5 antagonists in vitro. The detection of similar phenotypes in patients may identify those who could be at higher risk of virological failure on MVC.