Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co-receptor, CXCR4
| Autor: | Ikuhiko Nakase, Kazuki Shimane, Toshio Hattori, Yasuteru Sakurai, Masao Matsuoka, Yasuko Sakagami, Eiichi Kodama, Shiroh Futaki, Stefan G. Sarafianos, Xiaoguang Li |
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| Rok vydání: | 2010 |
| Předmět: |
chemistry.chemical_classification
Receptors CXCR4 Co-receptor Anti-HIV Agents viruses RNA Peptide HIV Infections rev Gene Products Human Immunodeficiency Virus Cell Biology Biology Flow Cytometry Virus Replication Biochemistry Molecular biology Virus Cell Line chemistry Viral replication Cytoplasm Cell culture HIV-1 Humans Antagonism Peptides |
| Zdroj: | The international journal of biochemistrycell biology. 42(9) |
| ISSN: | 1878-5875 |
| Popis: | Rev, a viral regulatory protein of HIV-1, binds through its arginine-rich domain to the Rev-responsive element (RRE), a secondary structure in transcribed HIV-1 RNA. Binding of Rev to RRE mediates export of singly spliced or unspliced mRNAs from the nucleus to the cytoplasm. It has been previously shown that a certain arginine-rich peptide exhibits not only RRE-binding ability but also cell permeability and antagonism of CXCR4, one of the major coreceptors of HIV-1. Here we designed and synthesized arginine-rich peptides derived from the RNA-binding domain of Rev (Rev(34-50)) and evaluated their anti-HIV-1 activities. Rev(34-50)-A(4)C, comprising Rev(34-50) with AAAAC at the C-terminus to increase the alpha-helicity, inhibited HIV-1 entry by CXCR4 antagonism and virus production in persistently HIV-1-infected PM1-CCR5 cells. Interestingly, similar motif of human lymphotropic virus type I Rex (Rex(1-21)) also exerted moderate anti-HIV-1 activity. These results indicate that arginine-rich peptide, Rev(34-50)-A(4)C exerts dual antagonism against CXCR4 and Rev. |
| Databáze: | OpenAIRE |
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