Effect of Mutations in the Human Immunodeficiency Virus Type 1 Protease on Cleavage of the gp41 Cytoplasmic Tail
| Autor: | Raymond C. Sowder, Abdul Waheed, Eric O. Freed, Carl P. Schaffner, Elena Chertova, James D. Roser, Sherimay D. Ablan |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Antifungal Agents
viruses medicine.medical_treatment Immunology Mutant Biology Cleavage (embryo) Gp41 Microbiology Virus HIV Protease Amphotericin B Virology Drug Resistance Viral medicine Humans HIV Protease Inhibitor chemistry.chemical_classification Protease Virion virus diseases HIV Protease Inhibitors Molecular biology HIV Envelope Protein gp41 Transmembrane protein Virus-Cell Interactions chemistry Insect Science Mutation HIV-1 Glycoprotein |
| Zdroj: | Journal of Virology. 84:3121-3126 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.02002-09 |
| Popis: | We previously reported that human immunodeficiency virus type 1 (HIV-1) develops resistance to the cholesterol-binding compound amphotericin B methyl ester (AME) by acquiring mutations (P203L and S205L) in the cytoplasmic tail of the transmembrane envelope glycoprotein gp41 that create cleavage sites for the viral protease (PR). In the present study, we observed that a PR inhibitor-resistant (PIR) HIV-1 mutant is unable to efficiently cleave the gp41 cytoplasmic tail in P203L and S205L virions, resulting in loss of AME resistance. To define the pathway to AME resistance in the context of the PIR PR, we selected for resistance with an HIV-1 isolate expressing the mutant enzyme. We identified a new gp41 mutation, R236L, that results in cleavage of the gp41 tail by the PIR PR. These results highlight the central role of gp41 cleavage as the primary mechanism of AME resistance. |
| Databáze: | OpenAIRE |
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