Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides
| Autor: | Ben Berkhout, Jeroen L. B. van Wamel, Leonie Beljaars, Servaas Visser, René Floris, Dirk K. F. Meijer |
|---|---|
| Přispěvatelé: | Nanomedicine & Drug Targeting, Medical Microbiology and Infection Prevention |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Receptors
CXCR4 GP120 ENVELOPE GLYCOPROTEIN Genes Viral electrostatic virus-cell interaction Antiviral protein TYPE-1 INFECTION Peptide CHEMOKINE RECEPTOR CXCR4 Virus Replication Antiviral Agents Cell Line chemistry.chemical_compound Viral envelope Viral Envelope Proteins Lactoferricin Viral entry milk protein DEXTRAN SULFATE Virology Casein Humans NEGATIVELY CHARGED ALBUMINS AMINO-TERMINAL DOMAIN Pharmacology chemistry.chemical_classification biology Lactoferrin V3 DOMAIN Biological activity IN-VITRO Milk Proteins Peptide Fragments chemistry Biochemistry HUMAN-IMMUNODEFICIENCY-VIRUS CORECEPTOR CCR5 Receptor Antagonists biology.protein antiviral activity HIV-1 |
| Zdroj: | Antiviral Research, 55(2):PII S0166-3542(02)00069-4, 341-355. ELSEVIER SCIENCE BV Antiviral research, 55(2), 341-355. Elsevier |
| ISSN: | 0166-3542 |
| Popis: | In a search for natural proteins with anti-HIV activity, we screened a large set of purified proteins from bovine milk and peptide fragments thereof. Because several charged proteins and peptides are known to inhibit the process of virus entry, we selected proteins with an unusual charge composition or hydrophobicity profile. In contrast with some chemically modified (strongly negative) milk proteins, unmodified alpha(s2)-, beta- and kappa-casein, as well as several negatively and positively charged fragments thereof, did not show significant inhibition of virus replication. In fact, HIV-1 replication was elevated in the presence of beta-casein or amphiphilic fragments thereof. Bovine lactoferrin (bLF), a milk protein of 80 kDa, showed considerable inhibitory activity against HIV-1 with an IC50 of 0.4 muM. Modest inhibition was obtained with lactoferricin, a highly positively charged loop domain of bLF, indicating that other domains within the native bLF protein may also be required for inhibition. bLF blocked HIV-1 variants that use either the CXCR4 or the CCR5 coreceptor. In order to obtain further insight into the mechanism of action of this antiviral protein, we selected a bLF-resistant HIV-1 variant. The bLF-resistance phenotype is mediated by the viral envelope protein, which contains two interesting mutations that have previously been associated with an altered virus-host interaction and a modified receptor-coreceptor interaction. These results demonstrate that bLF targets the HIV-1 entry process. (C) 2002 Elsevier Science B.V. All rights reserved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect