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Increased sensitivity of HIV variants selected by attachment inhibitors to broadly neutralizing antibodies.
- Source :
-
Virology [Virology] 2010 Jul 05; Vol. 402 (2), pp. 256-61. Date of Electronic Publication: 2010 Apr 18. - Publication Year :
- 2010
-
Abstract
- Treatment with HIV attachment inhibitors (AIs) can select for escape mutants throughout the viral envelope. We report on three such mutations: F423Y (gp120 CD4 binding pocket) and I595F and K655E (gp41 ectodomain). Each displayed decreased sensitivity to the AI BMS-488043 and earlier generation AIs, along with increased sensitivity to the broadly neutralizing antibodies 2F5 and 4E10, without affecting the rate of viral entry or sensitivity to the entry inhibitors AMD-3100 and Enfuvirtide. We also observed that I595F did not substantially increase envelope sensitivity to HIV-infected patient sera. Based on these observations, we propose that although F423Y, I595F and K655E may all affect the presentation of the 2F5 and 4E10 epitopes, natural immune mimicry is rare only for the I595F effect. Thus, it seems that in addition to restricting AI resistance development, incorporation of I595F into an appropriate vehicle could elicit a novel antiviral response to improve vaccine efficacy.<br /> (Copyright 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- HIV Envelope Protein gp120 genetics
HIV Envelope Protein gp120 immunology
HIV Envelope Protein gp41 genetics
HIV Envelope Protein gp41 immunology
HIV Fusion Inhibitors pharmacology
HIV-1 isolation & purification
Humans
Indoles
Molecular Structure
Neutralization Tests
Piperazines pharmacology
Pyruvic Acid
Antibodies, Neutralizing immunology
Drug Resistance, Viral
HIV Antibodies immunology
HIV Infections virology
HIV-1 drug effects
HIV-1 immunology
Mutation, Missense
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0341
- Volume :
- 402
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 20400170
- Full Text :
- https://doi.org/10.1016/j.virol.2010.03.033