Characterization of siamycin I, a human immunodeficiency virus fusion inhibitor
| Autor: | Bechtold Clifford M, A K Patick, Himadri Samanta, R J White, Richard J. Colonno, Ronald E. Rose, P.-F. Lin, Keith Riccardi, M. Alam, Carol Deminie |
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| Rok vydání: | 1996 |
| Předmět: |
T-Lymphocytes
viruses Molecular Sequence Data Biology medicine.disease_cause Antiviral Agents Membrane Fusion Virus Cell Line HIV Envelope Protein gp160 Myoblast fusion medicine Humans Pharmacology (medical) Pharmacology Mutation Cell fusion Base Sequence HIV virus diseases Lipid bilayer fusion Drug Resistance Microbial HIV envelope protein Virology In vitro Anti-Bacterial Agents Infectious Diseases Cell culture CD4 Antigens Intercellular Signaling Peptides and Proteins Peptides Reassortant Viruses Research Article HeLa Cells |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 40:133-138 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.40.1.133 |
| Popis: | The human immunodeficiency virus (HIV) fusion inhibitor siamycin I, a 21-residue tricyclic peptide, was identified from a Streptomyces culture by using a cell fusion assay involving cocultivation of HeLa-CD4+ cells and monkey kidney (BSC-1) cells expressing the HIV envelope gp160. Siamycin I is effective against acute HIV type 1 (HIV-1) and HIV-2 infections, with 50% effective doses ranging from 0.05 to 5.7 microM, and the concentration resulting in a 50% decrease in cell viability in the absence of viral infection is 150 microM in CEM-SS cells. Siamycin I inhibits fusion between C8166 cells and CEM-SS cells chronically infected with HIV (50% effective dose of 0.08 microM) but has no effect on Sendai virus-induced fusion or murine myoblast fusion. Siamycin I does not inhibit gp120 binding to CD4 in either gp120- or CD4-based capture enzyme-linked immunosorbent assays. Inhibition of HIV-induced fusion by this compound is reversible, suggesting that siamycin I binds noncovalently. An HIV-1 resistant variant was selected by in vitro passage of virus in the presence of increasing concentrations of siamycin I. Drug susceptibility studies on a chimeric virus containing the envelope gene from the siamycin I-resistant variant indicate that resistance maps to the gp160 gene. Envelope-deficient HIV complemented with gp160 from siamycin I-resistant HIV also displayed a resistant phenotype upon infection of HeLa-CD4-LTR-beta-gal cells. A comparison of the DNA sequences of the envelope genes from the resistant and parent viruses revealed a total of six amino acid changes. Together these results indicate that siamycin I interacts with the HIV envelope protein. |
| Databáze: | OpenAIRE |
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