Neutralization sensitivity of HIV-1 Env-pseudotyped virus clones is determined by co-operativity between mutations which modulate the CD4-binding site and those that affect gp120-gp41 stability
| Autor: | Carolina Herrera, Simon Beddows, Natalie N. Zheng, Elizabeth Michael, John P. Moore, Jonathan Weber, Rod S. Daniels, Kelly Barnes |
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| Rok vydání: | 2005 |
| Předmět: |
viruses
Mutant Molecular Sequence Data HIV Antibodies HIV Envelope Protein gp120 Gp41 Neutralization Virus CD4 binding site Envelope Neutralization Tests Virology Humans Binding site Antibody Infectivity chemistry.chemical_classification Binding Sites biology Mutants HIV Molecular biology gp41 HIV Envelope Protein gp41 Amino acid gp120 chemistry CD4 Antigens biology.protein HIV-1 |
| Zdroj: | Virology. 337(1) |
| ISSN: | 0042-6822 |
| Popis: | Adaptation of antibody neutralization-resistant human immunodeficiency virus type I (HIV-1) to growth in vitro generally results in the acquisition of a neutralization-sensitive phenotype, an alteration of viral growth kinetics, and an array of amino acid substitutions associated with these changes. Here we examine a panel of Env chimeras and mutants derived from these neutralization-resistant and -sensitive parental Envs. A range of neutralization and infectivity phenotypes was observed. These included a modulation of the CD4 binding site (CD4bs) towards recognition by neutralizing and non-neutralizing CD4bs-directed antibodies, resulting in a globally neutralization-sensitive Env; alterations which affected Env complex stability; and interactions which resulted in differential infectivity and CCR5/CXCR4 usage. This range of properties resulted from the complex interactions of no more than three amino acids found in key Env locations. These data add to a growing body of evidence that dramatic functional alterations of the native oligomeric Env protein complex can result from relatively minor amino acid substitutions. |
| Databáze: | OpenAIRE |
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