Epitope Switching as a Novel Escape Mechanism of HIV to CCR5 Monoclonal Antibodies

被引：5

作者：

Jekle, Andreas ^{[1
]}

Chhabra, Milloni ^{[1
]}

Lochner, Adriane ^{[1
]}

Meier, Sonja ^{[1
]}

Chow, Eugene ^{[1
]}

Brandt, Michael ^{[2
]}

Sankuratri, Surya ^{[1
]}

Cammack, Nick ^{[1
]}

Heilek, Gabrielle ^{[1
]}

机构：

[1] Roche Palo Alto LLC, Palo Alto, CA 94304 USA

[2] Roche Diagnost GmbH, Penzberg, Germany

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2010年 / 54卷 / 02期

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTORS; ANTIVIRAL ACTIVITY; HIGHLY POTENT; GP120; BINDING; TYPE-1; ENTRY; VIRAL ENTRY; INFECTION; INHIBITION; RESISTANCE;

D O I：

10.1128/AAC.00841-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

In passaging experiments, we isolated HIV strains resistant to MAb3952, a chemokine (C-C motif) receptor 5 (CCR5) monoclonal antibody (MAb) that binds to the second extracellular domain (extracellular loop 2 [ECL-2]) of CCR5. MAb3952-resistant viruses remain CCR5-tropic and are cross-resistant to a second ECL-2-specific antibody. Surprisingly, MAb3952-resistant viruses were more susceptible to RoAb13, a CCR5 antibody binding to the N terminus of CCR5. Using CCR5 receptor mutants, we show that MAb3952-resistant virus strains preferentially use the N terminus of CCR5, while the wild-type viruses preferentially use ECL-2. We propose this switch in the CCR5 binding site as a novel mechanism of HIV resistance.

引用

页码：734 / 741

页数：8

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