title: Paradoxical effects of two theta-defensins on HIV type 1 infection.
abstract: Retrocyclin-1 (RC-100) is a cyclic octadecapeptide whose primary structure is based on the sequence of an expressed human theta-defensin pseudogene. RC-111 has the same amino acid sequence as RC-100 and is also cyclic, but its residues are placed in reverse order along the peptide's backbone. We quantified the effects of RC-100 and RC-111 on HIV-1 infection using HIV clones that expressed green fluorescent protein. Whereas 0.2 microg/ml of RC-100 inhibited infection of CD4-positive cells by approximately 80%, its retro-analogue significantly enhanced infection of the cells. RC-100 and RC-111 also demonstrate their effects in HIV infection of CD4-negative cells. Whereas 40 ng/ml of RC-111 significantly enhanced infection of CD4-negative cells by HIV-1, RC-100 demonstrated significant inhibition of HIV infection with a concentration of approximately 10 microg/ml. RC-111ox, an acyclic variant of RC-111 with a beta-hairpin structure, also enhanced HIV-1 infection, but did so less effectively than cyclic RC-111. The divergent actions of RC-100 and RC-111 show that topology and polarity of theta-defensin peptides can determine their effect on HIV infection. The ability of RC-111 to enhance HIV-1 infection might prove useful in developing peptides that can enhance gene delivery by HIV-based lentiviral vectors.
authors.affiliation: UCLA School of Dentistry, and Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Qiuwei
authors.initials: Q
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Junying
authors.initials: J
authors.lastname: Zheng
authors.forename: Sina
authors.initials: S
authors.lastname: Tabibian
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Waring
authors.forename: Robert
authors.initials: R
authors.lastname: Chiu
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: Irvin S Y
authors.initials: IS
authors.lastname: Chen
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lehrer
authors.forename: Shen
authors.initials: S
authors.lastname: Pang
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002461:Cell Line, Transformed; D023082:Defensins / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000821:virology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology; D009457:Neuroglia / Q000821:virology*
chemical_list: D023082:Defensins; C450142:theta-defensin