Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41

被引：20

作者：

Anastasopoulou, Cleo G. ^{[1
]}

Ketas, Thomas J. ^{[1
]}

Depetris, Rafael S. ^{[1
]}

Thomas, Antonia M. ^{[1
]}

Klasse, Per Johan ^{[1
]}

Moore, John P. ^{[1
]}

机构：

[1] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA

来源：

VIROLOGY | 2011年 / 413卷 / 01期

关键词：

HIV-1; Entry inhibitors; Vicriviroc; Escape mutants; Fusion peptide; GPCR; V3; LOOP; ENTRY INHIBITORS; HIV-1; ANTAGONISTS; VICRIVIROC; INFECTIVITY; MUTATIONS; VARIANTS; TERMINUS; DYNAMICS;

D O I：

10.1016/j.virol.2010.12.052

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Here, we describe the genetic pathways taken by a human immunodeficiency virus type 1 (HIV-1) isolate, D101.12, to become resistant to the small molecule CCR5 inhibitor, vicriviroc (VCV), in vitro. Resistant D101.12 variants contained at least one substitution in the gp120 V3 region (H308P), plus one of two patterns of gp41 sequence changes involving the fusion peptide (FP) and a downstream residue: G514V+V535M or M518V+F519L+V535M. Studies of Env-chimeric and point-substituted viruses in peripheral blood mononuclear cells (PBMC) and TZM-bl cells showed that resistance can arise from the cooperative action of gp120 and gp41 changes, while retaining CCR5 usage. Modeling the VCV inhibition data from the two cell types suggests that D101.12 discriminates between high- and low-VCV affinity forms of CCR5 less than D1/85.16, a resistant virus with three FP substitutions. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：47 / 59

页数：13

共 34 条

[1] Adaptive Mutations in a Human Immunodeficiency Virus Type 1 Envelope Protein with a Truncated V3 Loop Restore Function by Improving Interactions with CD4 [J].

Agrawal-Gamse, Caroline ;

Lee, Fang-Hua ;

Haggarty, Beth ;

Jordan, Andrea P. O. ;

Yi, Yanjie ;

Lee, Benhur ;

Collman, Ronald G. ;

Hoxie, James A. ;

Doms, Robert W. ;

Laakso, Meg M. .

JOURNAL OF VIROLOGY, 2009, 83 (21) :11005-11015

[2] Escape of HIV-1 from a small molecule CCR5 inhibitor is not associated with a fitness loss [J].

Anastassopoulou, Cleo G. ;

Marozsan, Andre J. ;

Matet, Alexandre ;

Snyder, Amy D. ;

Arts, Eric J. ;

Kuhmann, Shawn E. ;

Moore, John P. .

PLOS PATHOGENS, 2007, 3 (06) :720-732

[3] Resistance to CCR5 inhibitors caused by sequence changes in the fusion peptide of HIV-1 gp41 [J].

Anastassopoulou, Cleo G. ;

Ketas, Thomas J. ;

Klasse, Per Johan ;

Moore, John P. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (13) :5318-5323

[4] Isolation and characterization of human immunodeficiency virus type 1 resistant to the small-molecule CCR5 antagonist TAK-652 [J].

Baba, Masanori ;

Miyake, Hiroshi ;

Wang, Xin ;

Okamoto, Mika ;

Takashima, Katsunori .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (02) :707-715

[5] Two HIV-1 Variants Resistant to Small Molecule CCR5 Inhibitors Differ in How They Use CCR5 for Entry [J].

Berro, Reem ;

Sanders, Rogier W. ;

Lu, Min ;

Klasse, Per J. ;

Moore, John P. .

PLOS PATHOGENS, 2009, 5 (08)

[6] Crystal Structure of HIV-1 gp41 Including Both Fusion Peptide and Membrane Proximal External Regions [J].

Buzon, Victor ;

Natrajan, Ganesh ;

Schibli, David ;

Campelo, Felix ;

Kozlov, Michael M. ;

Weissenhorn, Winfried .

PLOS PATHOGENS, 2010, 6 (05) :1-7

[7]

Coffin JM, 1996, AIDS, V10, pS75

[8] Selection of a Simian-Human Immunodeficiency Virus Strain Resistant to a Vaginal Microbicide in Macaques [J].

Dudley, Dawn M. ;

Wentzel, Jennifer L. ;

Lalonde, Matthew S. ;

Veazey, Ronald S. ;

Arts, Eric J. .

JOURNAL OF VIROLOGY, 2009, 83 (10) :5067-5076

[9] V3: HIV's switch-hitter [J].

Hartley, O ;

Klasse, PJ ;

Sattentau, QJ ;

Moore, JP .

AIDS RESEARCH AND HUMAN RETROVIRUSES, 2005, 21 (02) :171-189

[10] Antiretroviral drug resistance testing in adult HIV-1 infection:: 2008 recommendations of an International AIDS Society-USA panel [J].

Hirsch, Martin S. ;

Guenthard, Huldrych F. ;

Schapiro, Jonathan M. ;

Brun-Vezinet, Francoise ;

Clotet, Bonaventura ;

Hammer, Scott M. ;

Johnson, Victoria A. ;

Kuritzkes, Daniel R. ;

Mellors, John W. ;

Pillay, Deenan ;

Yeni, Patrick G. ;

Jacobsen, Donna M. ;

Richman, Douglas D. .

CLINICAL INFECTIOUS DISEASES, 2008, 47 (02) :266-285

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