Mutations in gp41 and gp120 of HIV-1 isolates resistant to hexa-arginine neomycin B conjugate

被引：14

作者：

Borkow, G ^{[1
]}

Lara, HH ^{[1
]}

Lapidot, A ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 312卷 / 04期

关键词：

HIV-1; aminoglycoside-arginme conjugates; viral entry; Gp120; Gp4l; mutations; heptad repeat;

D O I：

10.1016/j.bbrc.2003.11.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aminoglycoside-arginine conjugates (AACs) inhibit HIV-1 replication and act as Tat antagonists. AACs compete with monoclonal antibody binding to CXCR4, compete with SDF-1alpha and HIV-1 gp120 cellular uptake, indicating that they interfere with initial steps of HIV-1 infection. We here present the selection of HIV-1 isolates resistant to hexa-arginine neomycin B conjugate (NeoR6), the most potent anti-HIV-1 AAC. We found in the NeoR6-resistant isolates the following mutations in gp120: 1339T in the C3 region, S372L in the V4 region, and Q395K in the C4 region; and in gp41: S668R and F672Y in the 'heptad repeat' 2 (HR2) region. These findings strongly suggest that NeoR6 obstructs HIV-1 replication by interfering with the fusion step, dependent on both conformational changes in gp120 following CD4 and CXCR4 interaction, as well as by conformational changes in gp41 induced by HR1 and HR2 interaction. The AACs may thus represent a novel family of fusion inhibitors. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：1047 / 1052

页数：6

共 46 条

[1] Inhibiting HIV-1 entry with fusion inhibitors [J].

Baldwin, CE ;

Sanders, RW ;

Berkhout, B .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (17) :1633-1642

[2] Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease [J].

Berger, EA ;

Murphy, PM ;

Farber, JM .

ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :657-700

[3]

BORKOW G, 2003, IN PRESS ANTIVIRAL R

[4] Anti-human immunodeficiency virus activity of novel aminoglycoside-arginine conjugates at early stages of infection [J].

Cabrera, C ;

Gutiérrez, A ;

Blanco, J ;

Barretina, J ;

Litovchick, A ;

Lapidot, A ;

Evdokimov, AG ;

Clotet, B ;

Esté, JA .

AIDS RESEARCH AND HUMAN RETROVIRUSES, 2000, 16 (07) :627-634

[5] Anti-HIV activity of a novel aminoglycoside-arginine conjugate [J].

Cabrera, C ;

Gutiérrez, A ;

Barretina, J ;

Blanco, J ;

Litovchick, A ;

Lapidot, A ;

Clotet, B ;

Esté, JA .

ANTIVIRAL RESEARCH, 2002, 53 (01) :1-8

[6] Human immunodeficiency virus type 1 entry and chemokine receptors: a new therapeutic target [J].

Cammack, N .

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1999, 10 (02) :53-62

[7] Inhibition of protein synthesis by aminoglycoside-arginine conjugates [J].

Carriere, M ;

Vijayabaskar, V ;

Applefield, D ;

Harvey, I ;

Garneau, P ;

Lorsch, J ;

Lapidot, A ;

Pelletier, J .

RNA, 2002, 8 (10) :1267-1279

[8] The Tat antagonist neomycin B hexa-arginine conjugate inhibits gp-120-induced death of human neuroblastoma cells [J].

Catani, MV ;

Corasaniti, MT ;

Ranalli, M ;

Amantea, D ;

Litovchick, A ;

Lapidot, A ;

Melino, G .

JOURNAL OF NEUROCHEMISTRY, 2003, 84 (06) :1237-1245

[9] Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection [J].

Chackerian, B ;

Long, EM ;

Luciw, PA ;

Overbaugh, J .

JOURNAL OF VIROLOGY, 1997, 71 (05) :3932-3939

[10] Core structure of gp41 from the HIV envelope glycoprotein [J].

Chan, DC ;

Fass, D ;

Berger, JM ;

Kim, PS .

CELL, 1997, 89 (02) :263-273

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