Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co-receptor,CXCR4 |
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| Authors: | Kazuki Shimane Eiichi N. Kodama Ikuhiko Nakase Shiroh Futaki Yasuteru Sakurai Yasuko Sakagami Xiaoguang Li Toshio Hattori Stefan G. Sarafianos Masao Matsuoka |
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| Affiliation: | 1. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal;2. Centro de Análises Proteômicas e Bioquímicas, Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil;3. Programa de Pós-Graduação em Patologia Molecular, Universidade de Brasília, Brasília, DF, Brazil;4. S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil;5. Laboratory of Molecular Microbiology, Institute of Basic and Applied Microbiology, National University of Quilmes, Bernal, Buenos Aires, Argentina;6. Laboratory of Biointerfaces and Biomimetic Systems, CITSE, National University of Santiago del Estero-CONICET, Santiago del Estero, Argentina |
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| Abstract: | 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 (Rev34-50) and evaluated their anti-HIV-1 activities. Rev34-50-A4C, comprising Rev34-50 with AAAAC at the C-terminus to increase the α-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 (Rex1-21) also exerted moderate anti-HIV-1 activity. These results indicate that arginine-rich peptide, Rev34-50-A4C exerts dual antagonism against CXCR4 and Rev. |
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