title: Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co-receptor, CXCR4.
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 (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.
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Shimane
authors.forename: Eiichi N
authors.initials: EN
authors.lastname: Kodama
authors.forename: Ikuhiko
authors.initials: I
authors.lastname: Nakase
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Sakagami
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.forename: Toshio
authors.initials: T
authors.lastname: Hattori
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Sarafianos
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors*
chemical_list: D019380:Anti-HIV Agents; D010455:Peptides; D019718:Receptors, CXCR4; D054321:rev Gene Products, Human Immunodeficiency Virus